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  • 1.
    Adamsson, Viola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Influence of a healthy Nordic diet on serum fatty acid composition and associations with blood lipoproteins: results from the NORDIET study2014In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 58, p. 24114-Article in journal (Other academic)
    Abstract [en]

    Background: The fatty acid (FA) composition of serum lipids is related to the quality of dietary fat. The aim of this study was to investigate the effects of a healthy Nordic diet (ND) on the FA composition of serum cholesterol esters (CE-FA) and assess the associations between changes in the serum CE-FA composition and blood lipoproteins during a controlled dietary intervention.

    Methods: The NORDIET trial was a six-week randomised, controlled, parallel-group dietary intervention study that included 86 adults (53±8 years) with elevated low-density lipoprotein cholesterol LDL-C. Serum CE-FA composition was measured using gas chromatography. Diet history interviews were conducted, and daily intake was assessed using checklists.

    Results: Food and nutrient intake data indicated that there was a reduction in the fat intake from dairy and meat products and an increase in the consumption of fatty fish with the ND, decreasing the levels of saturated fatty acids (SFA) in the diet, slightly decreasing the levels of monounsaturated fatty acids (MUFA) and moderately increasing the levels of polyunsaturated fatty acids (PUFA). Concomitantly, the levels of CE-SFA 14:0, 15:0 and 18:0, but not 16:0, decreased during the ND, and these changes differed from those observed in the control diet group (p<0.01). In contrast, serum 22:6n-3 increased during the ND compared with the control diet (p<0.01). The changes in CE-SFA 14:0, 15:0 and 18:0 during the intervention correlated positively with those in LDL-C, HDL-C, LDL-C/HDL-C, ApoA1 and ApoB (p<0.01), whereas the changes in CE-PUFA 22:6n-3 were negatively correlated with changes in the corresponding serum lipids.

    Conclusions: The decreased intake of saturated fat and increased intake of n-3 PUFA in a healthy Nordic diet are partly reflected by changes in the serum CE-FA composition, which are associated with an improved serum lipoprotein pattern.

  • 2.
    Adamsson, Viola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Reumark, Anna
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Johansson, Gunnar
    What is a healthy Nordic diet?: Foods and nutrients in the NORDIET study2012In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 56, p. 18189-Article in journal (Refereed)
    Abstract [en]

    Background: A healthy Nordic diet (ND), a diet based on foods originating from the Nordic countries, improves blood lipid profile and insulin sensitivity and lowers blood pressure and body weight in hypercholesterolemic subjects. Objective: To describe and compare food and nutrient composition of the ND in relation to the intake of a Swedish reference population (SRP) and the recommended intake (RI) and average requirement (AR), as described by the Nordic nutrition recommendations (NNR). Design: The analyses were based on an estimate of actual food and nutrient intake of 44 men and women (mean age 53 +/- 8 years, BMI 26 +/- 3), representing an intervention arm receiving ND for 6 weeks. Results: The main difference between ND and SRP was the higher intake of plant foods, fish, egg and vegetable fat and a lower intake of meat products, dairy products, sweets and desserts and alcoholic beverages during ND (p<0.001 for all food groups). Intake of cereals and seeds was similar between ND and SRP (p>0.3). The relative intake of protein, fat and carbohydrates during ND was in accordance with RI. Intake of all vitamins and minerals was above AR, whereas sodium intake was below RI. Conclusions: When compared with the food intake of an SRP, ND is primarily a plant-based diet. ND represents a balanced food intake that meets the current RI and AR of NNR 2004 and has a dietary pattern that is associated with decreased morbidity and mortality.

  • 3.
    Adamsson, Viola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Reumark, Anna
    Lantmännen.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Role of a prudent breakfast in improving cardiometabolic risk factors in subjects with hypercholesterolemia: a randomized controlled trialArticle in journal (Other academic)
    Abstract [en]

    Background & Aims: It is unclear whether advising a prudent breakfast alone is sufficient to improve blood lipids and cardiometabolic risk factors in overweight hypercholesterolemic subjects.

    Methods: The aim of the present study was to investigate whether a prudent low-fat breakfast (PB) rich in dietary fiber lowers low-density lipoprotein cholesterol (LDL-C) and other cardiometabolic risk factors in subjects with elevated LDL-cholesterol levels. In a parallel, controlled, 12-week study, 79 healthy overweight subjects (all regular breakfast eaters) were randomly allocated to a group that received a PB based on Nordic foods provided ad libitum or a control group that consumed their usual breakfast. The PB was in accordance with national and Nordic nutrition recommendations and included oat bran porridge with low-fat milk or yogurt, bilberry or lingonberry jam, whole grain bread, low-fat spread, poultry or fatty fish, and fruit.

    Results: No differences were found in LDL-C, blood lipids, body weight, or glucose metabolism, but SAD, plasma CRP, and TNF-R2 were lower during PB compared with controls (p<0.05). In the overall diet, PB increased dietary fiber and b-glucan compared with controls (p<0.05).

    Conclusions: Advising a prudent breakfast for 3 months did not influence blood lipids, body weight, or glucose metabolism but reduced markers of visceral fat and inflammation.

     

  • 4.
    Adamsson, Viola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Reumark, Anna
    Marklund, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Role of a prudent breakfast in improving cardiometabolic risk factors in subjects with hypercholesterolemia: A randomized controlled trial2015In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 34, no 1, p. 20-26Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS:

    It is unclear whether advising a prudent breakfast alone is sufficient to improve blood lipids and cardiometabolic risk factors in overweight hypercholesterolemic subjects. The aim of this study was to investigate whether a prudent low-fat breakfast (PB) rich in dietary fiber lowers low-density lipoprotein cholesterol (LDL-C) and other cardiometabolic risk factors in subjects with elevated LDL-cholesterol levels.

    METHODS:

    In a parallel, controlled, 12-week study, 79 healthy overweight subjects (all regular breakfast eaters) were randomly allocated to a group that received a PB based on Nordic foods provided ad libitum or a control group that consumed their usual breakfast. The primary outcome was plasma LDL-C. Secondary outcomes were other blood lipids, body weight, sagittal abdominal diameter (SAD), glucose tolerance, insulin sensitivity and inflammation markers (C-reactive protein [CRP] and tumor necrosis factor receptor-2 [TNF-R2]), and blood pressure. The PB was in accordance with national and Nordic nutrition recommendations and included oat bran porridge with low-fat milk or yogurt, bilberry or lingonberry jam, whole grain bread, low-fat spread, poultry or fatty fish, and fruit.

    RESULTS:

    No differences were found in LDL-C, other blood lipids, body weight, or glucose metabolism, but SAD, plasma CRP, and TNF-R2 decreased more during PB compared with controls (p < 0.05). In the overall diet, PB increased dietary fiber and β-glucan compared with controls (p < 0.05).

    CONCLUSIONS:

    Advising a prudent breakfast for 3 months did not influence blood lipids, body weight, or glucose metabolism but reduced markers of visceral fat and inflammation. The trial was registered in the Current Controlled Trials database (http://www.controlled-trials.com); International Standard Randomized Controlled Trial Number (ISRCTN): 84550872.

  • 5.
    Alsharari, Zayed
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Marklund, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Hellenius, Mai-Lis
    Karolinska Inst, Inst Environm Med, Cardiovasc Epidemiol Unit, S-10401 Stockholm, Sweden..
    Laguzzi, Federica
    Karolinska Inst, Inst Environm Med, Cardiovasc Epidemiol Unit, S-10401 Stockholm, Sweden..
    Gigante, Bruna
    Karolinska Inst, Inst Environm Med, Cardiovasc Epidemiol Unit, S-10401 Stockholm, Sweden..
    Leander, Karen
    Karolinska Inst, Inst Environm Med, Cardiovasc Epidemiol Unit, S-10401 Stockholm, Sweden..
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Cardiovasc Epidemiol Unit, S-10401 Stockholm, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Serum Biomarkers of Dietary Fatty Acids are Associated with Abdominal Obesity Measures in a Large Population-based Cohort of Men and Women2015In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 29, no 1 SupplementArticle in journal (Other academic)
  • 6.
    Alsharari, Zayed
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Leander, Karin
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carlsson, Axel C.
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Vikstrom, Max
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Laguzzi, Federica
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Gigante, Bruna
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden.;Karolinska Inst, Danderyds Hosp, Div Cardiovasc Med, Dept Clin Sci, Stockholm, Sweden..
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    De Faire, Ulf
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Hellenius, Mai-Lis
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Marklund, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Serum Fatty Acids, Desaturase Activities and Abdominal Obesity - A Population-Based Study of 60-Year Old Men and Women2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0170684Article in journal (Refereed)
    Abstract [en]

    Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA- desaturase and Delta 6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, alpha-linolenic acid, docohexaenoic acid, and Delta 5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the contrary was true for linoleic acid. Further trials should examine the potential role of linoleic acid and its main dietary source, vegetable oils, in abdominal obesity prevention.

  • 7. Andersson, Daniel P.
    et al.
    Thorell, Anders
    Lofgren, Patrik
    Wiren, Mikael
    Toft, Eva
    Qvisth, Veronica
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Berglund, Lars
    Naslund, Erik
    Bringman, Sven
    Thorne, Anders
    Arner, Peter
    Hoffstedt, Johan
    Omentectomy in addition to gastric bypass surgery and influence on insulin sensitivity: A randomized double blind controlled trial2014In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 33, no 6, p. 991-996Article in journal (Refereed)
    Abstract [en]

    Background & aims: Accumulation of visceral adipose tissue is associated with insulin resistance and cardio-vascular disease. The aim of this study was to elucidate whether removal of a large amount of visceral fat by omentectomy in conjunction with Roux en-Y gastric bypass operation (RYGB) results in enhanced improvement of insulin sensitivity compared to gastric bypass surgery alone. Methods: Eighty-one obese women scheduled for RYGB were included in the study. They were randomized to RYGB or RYGB in conjunction with omentectomy. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp before operation and sixty-two women were also reexamined 2 years post-operatively. The primary outcome measure was insulin sensitivity and secondary outcome measures included cardio-metabolic risk factors. Results: Two-year weight loss was profound but unaffected by omentectomy. Before intervention, there were no clinical or metabolic differences between the two groups. The difference in primary outcome measure, insulin sensitivity, was not significant between the non-omentectomy (6.7 +/- 1.6 mg/kg body weight/minute) and omentectomy groups (6.6 +/- 1.5 mg/kg body weight/minute) after 2 years. Nor did any of the cardio-metabolic risk factors that were secondary outcome measures differ significantly. Conclusion: Addition of omentectomy to gastric bypass operation does not give an incremental effect on long term insulin sensitivity or cardio-metabolic risk factors. The clinical usefulness of omentectomy in addition to gastric bypass operation is highly questionable.

  • 8.
    Arnlöv, Johan
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lind, Lars
    Department of Medical Sciences.
    Andrén, Bertil
    Department of Medical Sciences.
    Riserus, U
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berglund, L
    Lithell, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    A Doppler-derived index of combined left ventricular systolic and diastolic function is an independent predictor of cardiovascular mortality in elderly men.2005In: Am Heart J, ISSN 1097-6744, Vol. 149, no 5, p. 902-7Article in journal (Refereed)
  • 9.
    Basu, Samar
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Smedman, Annika
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Risérus, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Vessby, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Conjugated linoleic acid (CLA) induces lipid perxidation in humans2000In: Proceedings if the OCC Meeting 2000, 2000Conference paper (Refereed)
  • 10.
    Bjermo, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Ingrid
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Persson, Lena
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Pulkki, Kari
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Uusitupa, Matti
    Rudling, Mats
    Arner, Peter
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial2012In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 95, no 5, p. 1003-1012Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Replacing SFAs with vegetable PUFAs has cardiometabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs have, however, also been proposed to promote inflammation-a yet unproven theory.

    OBJECTIVE:

    We investigated the effects of PUFAs on liver fat, systemic inflammation, and metabolic disorders.

    DESIGN:

    We randomly assigned 67 abdominally obese subjects (15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet), without altering the macronutrient intake. Liver fat was assessed by MRI and magnetic resonance proton (1H) spectroscopy (MRS). Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic LDL-receptor regulator), inflammation, and adipose tissue expression of inflammatory and lipogenic genes were determined.

    RESULTS:

    A total of 61 subjects completed the study. Body weight modestly increased but was not different between groups. Liver fat was lower during the PUFA diet than during the SFA diet [between-group difference in relative change from baseline; 16% (MRI; P < 0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2 (P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were lower during the PUFA diet, whereas insulin (P = 0.06) tended to be higher during the SFA diet. In compliant subjects (defined as change in serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides were lower during the PUFA diet than during the SFA diet (P < 0.05). Adipose tissue gene expression was unchanged.

    CONCLUSIONS:

    Compared with SFA intake, n-6 PUFAs reduce liver fat and modestly improve metabolic status, without weight loss. A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress. Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs.

  • 11.
    Bjermo, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Should dietary SFA be exchanged for linoleic acid?: Reply2012In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 96, no 4, p. 945-946Article in journal (Refereed)
  • 12. Brader, Lea
    et al.
    Rejnmark, Lars
    Carlberg, Carsten
    Schwab, Ursula
    Kolehmainen, Marjukka
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cloetens, Lieselotte
    Landin-Olsson, Mona
    Gunnarsdottir, Ingibjorg
    Poutanen, Kaisa S.
    Herzig, Karl-Heinz
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Savolainen, Markku J.
    Thorsdottir, Inga
    Uusitupa, Matti
    Hermansen, Kjeld
    Effects of a healthy Nordic diet on plasma 25-hydroxyvitamin D concentration in subjects with metabolic syndrome: a randomized, placebo-controlled trial (SYSDIET)2014In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 53, no 4, p. 1123-1134Article in journal (Refereed)
    Abstract [en]

    At northern latitudes, vitamin D is not synthesized endogenously during winter, causing low plasma 25-hydroxyvitamin D (25(OH)D) concentrations. Therefore, we evaluated the effects of a healthy Nordic diet based on Nordic nutrition recommendations (NNR) on plasma 25(OH)D and explored its dietary predictors. In a Nordic multi-centre trial, subjects (n = 213) with metabolic syndrome were randomized to a control or a healthy Nordic diet favouring fish (a parts per thousand yen300 g/week, including a parts per thousand yen200 g/week fatty fish), whole-grain products, berries, fruits, vegetables, rapeseed oil and low-fat dairy products. Plasma 25(OH)D and parathyroid hormone were analysed before and after 18- to 24-week intervention. At baseline, 45 % had vitamin D inadequacy (< 50 nmol/l), whereas 8 % had deficiency (< 25 nmol/l). Dietary vitamin D intake was increased by the healthy Nordic diet (P < 0.001). The healthy Nordic and the control diet reduced the prevalence of vitamin D inadequacy by 42 % (P < 0.001) and 19 % (P = 0.002), respectively, without between-group difference (P = 0.142). Compared with control, plasma 25(OH)D (P = 0.208) and parathyroid hormone (P = 0.207) were not altered by the healthy Nordic diet. Predictors for 25(OH)D were intake of vitamin D, eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA), vitamin D supplement, plasma EPA and plasma DHA. Nevertheless, only vitamin D intake and season predicted the 25(OH)D changes. Consuming a healthy Nordic diet based on NNR increased vitamin D intake but not plasma 25(OH)D concentration. The reason why fish consumption did not improve vitamin D status might be that many fish are farmed and might contain little vitamin D or that frying fish may result in vitamin D extraction. Additional ways to improve vitamin D status in Nordic countries may be needed.

  • 13. Carlsson, A. C.
    et al.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Engstrom, G.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Melander, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Leander, K.
    Gigante, B.
    Hellenius, M-L
    de Faire, U.
    Novel and established anthropometric measures and the prediction of incident cardiovascular disease: a cohort study2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 12, p. 1579-1585Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to compare novel and established anthropometrical measures in their ability to predict cardiovascular disease (CVD), and to determine whether they improve risk prediction beyond classical risk factors in a cohort study of 60-year-old men and women. We also stratified the results according to gender to identify possible differences between men and women. Furthermore, we aimed to replicate our findings in a large independent cohort (The Malmo Diet and Cancer study-cardiovascular cohort). METHODS: This was a population-based study of 1751 men and 1990 women, aged 60 years and without CVD at baseline, with 375 incident cases of CVD during 11 years of follow-up. Weight, height, waist circumference (WC), hip circumference and sagittal abdominal diameter (SAD) were measured at baseline. Body mass index (BMI), waist-hip ratio (WHR), waist-hip-height ratio (WHHR), WC-to-height ratio (WCHR) and SAD-to-height ratio (SADHR) were calculated. RESULTS: All anthropometric measures predicted CVD in unadjusted Cox regression models per s.d. increment (hazard ratios, 95% confidence interval), while significant associations after adjustments for established risk CVD factors were noted for WHHR 1.20 (1.08-1.33), WHR 1.14 (1.02-1.28), SAD 1.13 (1.02-1.25) and SADHR 1.17 (1.06-1.28). WHHR had higher increases in C-statistics, and model improvements (likelihood ratio tests (P<0.001)). In the replication study (MDC-CC, n = 5180), WHHR was the only measure that improved Cox regression models in men (P = 0.01). CONCLUSION: WHHR, a new measure reflecting body fat distribution, showed the highest risk estimates after adjustments for established CVD risk factors. These findings were verified in men but not women in an independent cohort.

  • 14. Carlsson, A. C.
    et al.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Borne, Y.
    Leander, K.
    Gigante, B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Hellenius, M. -L
    Bottai, M.
    de Faire, U.
    Prediction of cardiovascular disease by abdominal obesity measures is dependent on body weight and sex - Results from two community based cohort studies2014In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 24, no 8, p. 891-899Article in journal (Refereed)
    Abstract [en]

    Aim: To study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men and women stratified by BMI (cut-off >= 25). Methods and results: A cohort of n = 3741 (53% women) 60-year old individuals without CVD was followed for 11-years (375 CVD cases). To replicate the results, we also assessed another large independent cohort; The Malmo Diet and Cancer study - cardiovascular cohort (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for established risk factors in normal-weight women, the hazard ratio (HR) per one standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35-2.70), WC; 1.81 (95% CI 1.02-3.20), SAD; 1.25 (95% CI 0.74-2.11), and WHHR; 1.97 (95% CI 1.40-2.78). In men the association with WHR, WHHR and WC were not significant, whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19 (95% CI 1.04-1.35). After adjustments for established risk factors in overweight/obese women, none of the measures were significantly associated with CVD risk. In men, however, all measures were significant predictors; WHR; 1.24 (955 CI 1.04-1.47), WC 1.19 (95% CI 1.00-1.42), SAD 1.21 (95% CI 1.00-1.46), and WHHR; 1.23 (95% CI 1.05-1.44). Only the findings in men with BMI >= 25 were verified in MDCC. Conclusion: In normal weight individuals, WHHR and WHR were the best predictors in women, whereas SAD was the only independent predictor in men. Among overweight/obese individuals all measures failed to predict CVD in women, whereas WHHR was the strongest predictor after adjustments for CVD risk factors in men.

  • 15.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Calamia, Michael
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kidney injury molecule (KIM)-1 is associated with insulin resistance: Results from two community-based studies of elderly individuals2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 103, no 3, p. 516-521Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.

    DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).

    RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.

    CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.

  • 16.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hypertriglyceridemic Waist Phenotype Is Associated with Decreased Insulin Sensitivity and Incident Diabetes in Elderly Men2014In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, no 2, p. 526-529Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the association between hypertriglyceridemic waist (HTGW) and insulin sensitivity (assessed by euglycemic clamp method), and the development of diabetes in a longitudinal community-based cohort of elderly men without diabetes at baseline. Design and Methods: The present cross-sectional study comprised 1,026, 70-year-old men without diabetes. The gold standard euglycaemic-hyperinsulinaemic clamp technique was used. Six-year follow-up on diabetes status were available in n = 667. The HTGW phenotype was defined as having waist circumference >= 90 cm, and triglycerides >= 2 mmol L-1. The men were stratified into those having normal WC and TG (n = 299), one HTGW component (n = 606), and HTGW (n = 121). Results: The association between insulin sensitivity and one HTGW component as well as HTGW was highly significant (P < 0.001) in the whole sample, as well as in individuals with high/low BMI (stratified at >= 25). In longitudinal analyses, participants with HTGW was associated with a more than fourfold increased risk for diabetes (Odds ratio 4.64, 95% CI 1.61-13.4, P = 0.004) compared to those with normal WC and TG. Conclusion: The present study both confirm and extend previous research suggesting that the HTGW-phenotype portrays an increased glucometabolic risk, also in lean individuals.

  • 17.
    Carlsson, Axel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wändell, Per
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Borné, Yan
    Engström, Gunnar
    Leander, Karin
    Gigante, Bruna
    Hellenius, Mai-Lis
    de Faire, Ulf
    Differences inanthropometric measures in immigrants and Swedish-born individuals: Results from two community based cohort studies2014In: Preventive Medicine, ISSN 0091-7435, E-ISSN 1096-0260, Vol. 69, p. 151-156Article in journal (Refereed)
    Abstract [en]

    Aim

    To study differences in body mass index (BMI), waist–hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), waist–hip–height ratio (WHHR) and percent body fat in immigrants and Swedish-born men and women in two large population-based samples.

    Methods

    A cross-sectional analysis of 60-year-old individuals, n = 4 232. To replicate the results, we also assessed another large independent cohort cross-sectionally, the Malmö Diet and Cancer Study (MDC, n = 26 777). The data from both cohorts were collected in the 1990s in Sweden.

    Results

    Significant differences between Finnish-born, Middle Eastern and women from the rest of the world were seen for all anthropometric measures, using Swedish-born women as referent. However, WHHR was the only anthropometric measure that identified all these three groups of immigrant women as different from Swedish-born women with high statistical certainty (p < 0.001). Apart from WHHR that identified differences in anthropometry in all immigrant groups of men using Swedish-born men as referent, few significant differences were seen in anthropometry among groups of immigrant men. These finding were observed in both cohorts, and remained after adjustments for smoking, physical activity and educational level.

    Conclusion

    The present study confirms previous findings of more obesity among immigrants and is the first to report that WHHR measurements may detect anthropometric differences between different ethnic groups better than other anthropometrical measures.

  • 18. Carrero, Juan J.
    et al.
    Huang, Xiaoyan
    Jimenez-Moleon, Jose
    Lindholm, Bengt
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Arnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Mediterranean Diet, Kidney Function, And Mortality In Men With Chronic Kidney Disease2013In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 28, no S1, p. 8-8Article in journal (Other academic)
  • 19.
    Caruso, Vanni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Tasmania UTAS, Fac Pharm, Hobart, Tas 7001, Australia..
    Sreedharan, Smitha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Carlini, Valeria P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Nacl Cordoba, Fac Ciencias Quim Haya Torre & Medina Allende, Dept Farmacol, Ciudad Univ, RA-5016 Cordoba, Argentina..
    Jacobsson, Josefin A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Haitina, Tatjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hammer, Joanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stephansson, Olga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Crona, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sommer, Wolfgang H.
    Cent Inst Mental Hlth, Dept Psychopharmacol, Mannheim, Germany..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Marcus, Claude
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Natl Childhood Obes Ctr, Div Pediat, Stockholm, Sweden..
    Heilig, Markus
    NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA..
    de Barioglio, Susana R.
    Univ Nacl Cordoba, Fac Ciencias Quim Haya Torre & Medina Allende, Dept Farmacol, Ciudad Univ, RA-5016 Cordoba, Argentina..
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    mRNA GPR162 changes are associated with decreased food intake in rat, and its human genetic variants with impairments in glucose homeostasis in two Swedish cohorts2016In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 581, no 2, p. 139-145Article in journal (Refereed)
    Abstract [en]

    G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized. Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding. In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis.

  • 20.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Alsiö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Västermark, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Adipose tissue stearoyl-CoA desaturase 1 index is increased and linoleic acid is decreased in obesity-prone rats fed a high-fat diet2013In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 12, no 2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Fatty acid (FA) composition and desaturase indices are associated with obesity and related metabolic conditions. However, it is unclear to what extent desaturase activity in different lipid fractions contribute to obesity susceptibility. Our aim was to test whether desaturase activity and FA composition are linked to an obese phenotype in rats that are either obesity prone (OP) or resistant (OR) on a high-fat diet (HFD).

    METHODS

    Two groups of Sprague-Dawley rats were given ad libitum (AL-HFD) or calorically restricted (HFD-paired; pair fed to calories consumed by chow-fed rats) access to a HFD. The AL-HFD group was categorized into OP and OR sub-groups based on weight gain over 5 weeks. Five different lipid fractions were examined in OP and OR rats with regard to proportions of essential and very long-chain polyunsaturated FAs: linoleic acid (LA), alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and the stearoyl-CoA desaturase 1 (SCD-1) product 16:1n-7. FA ratios were used to estimate activities of the delta-5-desaturase (20:4n-6/20:3n-6), delta-6-desaturase (18:3n-6/18:2n-6), stearoyl-CoA desaturase 1 (SCD-1; 16:1n-7/16:0, SCD-16 and 18:1n-9/18:0, SCD-18), de novo lipogenesis (16:0/18:2n-6) and FA elongation (18:0/16:0). Fasting insulin, glucose, adiponectin and leptin concentrations were measured in plasma.

    RESULTS

    After AL-HFD access, OP rats had a significantly higher SCD-16 index and 16:1n-7 proportion, but a significantly lower LA proportion, in subcutaneous adipose tissue (SAT) triacylglycerols, as well as significantly higher insulin and leptin concentrations, compared with OR rats. No differences were found between the two phenotypes in liver (phospholipids; triacylglycerols) or plasma (cholesterol esters; phospholipids) lipid fractions or for plasma glucose or adiponectin concentrations. For the desaturase indices of the HFD-paired rats, the only significant differences compared with the OP or OR rats were higher SCD-16 and SCD-18 indices in SAT triacylglycerols in OP compared with HFD-paired rats.

    CONCLUSION

    The higher SCD-16 may reflect higher SCD-1 activity in SAT, which in combination with lower LA proportions may reflect higher insulin resistance and changes in SAT independent of other lipid fractions. Whether a lower SCD-16 index protects against diet-induced obesity is an interesting possibility that warrants further investigation.

  • 21. Delgado-Lista, J.
    et al.
    Perez-Martinez, P.
    Garcia-Rios, A.
    Phillips, C. M.
    Hall, W.
    Gjelstad, I. M. F.
    Lairon, D.
    Saris, W.
    Kiec-Wilk, B.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Drevon, C. A.
    Defoort, C.
    Blaak, E. E.
    Dembinska-Kiec, A.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lovegrove, J. A.
    Roche, H. M.
    Lopez-Miranda, J.
    A gene variation (rs12691) in the CCAT/enhancer binding protein alpha modulates glucose metabolism in metabolic syndrome2013In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 23, no 5, p. 417-423Article in journal (Refereed)
    Abstract [en]

    Background and aims: CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients. Methods and results: Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration. Conclusion: The presence of the A allele of rs12691 influences glucose metabolism of MetS patients. Clinical Trials Registry number NCT00429195.

  • 22. Delgado-Lista, Javier
    et al.
    Perez-Martinez, Pablo
    Solivera, Juan
    Garcia-Rios, Antonio
    Perez-Caballero, A. I.
    Lovegrove, Julie A.
    Drevon, Christian A.
    Defoort, Catherine
    Blaak, Ellen E.
    Dembinska-Kiec, Aldona
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Herruzo-Gomez, Ezequiel
    Camargo, Antonio
    Ordovas, Jose M.
    Roche, Helen
    Lopez-Miranda, Jose
    Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome: From the LIPGENE Study2014In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 2, p. E384-E389Article in journal (Refereed)
    Abstract [en]

    Rationale: Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Objectives: Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. Methods: A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. Findings: From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). Conclusions: We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

  • 23.
    Dragsted, L.
    et al.
    Univ Copenhagen, Dept Nutr Exercise & Sports, DK-1168 Copenhagen, Denmark..
    Acar, E.
    Univ Copenhagen, Dept Food Sci, DK-1168 Copenhagen, Denmark..
    Gurdeniz, G.
    Univ Copenhagen, Dept Nutr Exercise & Sports, DK-1168 Copenhagen, Denmark..
    Andersen, M-B
    Univ Copenhagen, Dept Nutr Exercise & Sports, DK-1168 Copenhagen, Denmark..
    Poulsen, S.
    Univ Copenhagen, Dept Nutr Exercise & Sports, DK-1168 Copenhagen, Denmark..
    Astrup, A.
    Univ Copenhagen, Dept Nutr Exercise & Sports, DK-1168 Copenhagen, Denmark..
    Bro, R.
    Univ Copenhagen, Dept Food Sci, DK-1168 Copenhagen, Denmark..
    Engelsen, S. B.
    Univ Copenhagen, Dept Food Sci, DK-1168 Copenhagen, Denmark..
    Savorani, F.
    Univ Copenhagen, Dept Food Sci, DK-1168 Copenhagen, Denmark..
    Brader, L.
    Aarhus Univ Hosp, Dept Med & Endocrinol MEA, Aarhus, Denmark..
    Hermansen, K.
    Aarhus Univ Hosp, Dept Med & Endocrinol MEA, Aarhus, Denmark..
    Schwab, U.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Joensuu, Finland..
    Kolehmainen, M.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Joensuu, Finland..
    Paananen, J.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Joensuu, Finland..
    Poutanen, K. S.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Joensuu, Finland..
    Cloetens, L.
    Lund Univ, Biomed Nutr Pure & Appl Biochem, S-22100 Lund, Sweden..
    Akesson, B.
    Lund Univ, Biomed Nutr Pure & Appl Biochem, S-22100 Lund, Sweden..
    Siloaho, M.
    Univ Oulu, Dept Internal Med, Inst Clin Med, SF-90100 Oulu, Finland..
    Savolainen, M. J.
    Univ Oulu, Dept Internal Med, Inst Clin Med, SF-90100 Oulu, Finland..
    Gunnarsdottir, I
    Univ Iceland, IS-101 Reykjavik, Iceland.;Natl Univ Hosp Iceland, Landspitali, Reykjavik, Iceland..
    Thorsdottir, I
    Univ Iceland, IS-101 Reykjavik, Iceland.;Natl Univ Hosp Iceland, Landspitali, Reykjavik, Iceland..
    Ulven, S. M.
    Oslo & Akershus Univ Coll Appl Sci, Fac Hlth Sci, Dept Hlth Nutr & Management, Oslo, Norway..
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Uusitupa, M.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Joensuu, Finland..
    Larsen, T. M.
    Univ Copenhagen, Dept Nutr Exercise & Sports, DK-1168 Copenhagen, Denmark..
    Metabolomic response to Nordic foods2015In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 67, p. 55-55Article in journal (Other academic)
  • 24.
    Elmsjö, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Engskog, Mikael K R
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Haglöf, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arvidsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Pettersson, Curt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass.2015In: Nutrition & Diabetes, ISSN 2044-4052, E-ISSN 2044-4052, Vol. 5, no 19, p. e182-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Overeating different dietary fatty acids influence the amount of liver fat stored during weight gain, however, the mechanisms responsible are unclear. We aimed to identify non-lipid metabolites that may differentiate between saturated (SFA) and polyunsaturated fatty acid (PUFA) overfeeding using a non-targeted metabolomic approach. We also investigated the possible relationships between plasma metabolites and body fat accumulation.

    METHODS: In a randomized study (LIPOGAIN study), n=39 healthy individuals were overfed with muffins containing SFA or PUFA. Plasma samples were precipitated with cold acetonitrile and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Pattern recognition techniques were used to overview the data, identify variables contributing to group classification and to correlate metabolites with fat accumulation.

    RESULTS: We previously reported that SFA causes a greater accumulation of liver fat, visceral fat and total body fat, whereas lean tissue levels increases less compared with PUFA, despite comparable weight gain. In this study, lactate and acetate were identified as important contributors to group classification between SFA and PUFA (P<0.05). Furthermore, the fat depots (total body fat, visceral adipose tissue and liver fat) and lean tissue correlated (P(corr)>0.5) all with two or more metabolites (for example, branched amino acids, alanine, acetate and lactate). The metabolite composition differed in a manner that may indicate higher insulin sensitivity after a diet with PUFA compared with SFA, but this needs to be confirmed in future studies.

    CONCLUSION: A non-lipid metabolic profiling approach only identified a few metabolites that differentiated between SFA and PUFA overfeeding. Whether these metabolite changes are involved in depot-specific fat storage and increased lean tissue mass during overeating needs further investigation.

  • 25. Erkkilä, Arja
    et al.
    de Mello, Vanessa D F
    Risérus, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Laaksonen, David E
    Dietary fatty acids and cardiovascular disease: An epidemiological approach.2008In: Prog Lipid Res, ISSN 0163-7827, Vol. 47, no 3, p. 172-87Article in journal (Refereed)
  • 26.
    Fallaize, R.
    et al.
    Univ Reading, Hugh Sinclair Unit Human Nutr, Reading RG6 6AP, Berks, England.;Univ Reading, Inst Cardiovasc & Metab Res, Reading RG6 6AP, Berks, England..
    Carvalho-Wells, A. L.
    Univ Reading, Hugh Sinclair Unit Human Nutr, Reading RG6 6AP, Berks, England.;Univ Reading, Inst Cardiovasc & Metab Res, Reading RG6 6AP, Berks, England..
    Ayres, K.
    Univ Reading, Dept Math & Stat, Reading RG6 6AP, Berks, England..
    Dembinska-Kiec, A.
    Univ Med Coll, Dept Clin Biochem, Krakow, Poland..
    Drevon, C. A.
    Oslo Univ Hosp Oslo, Dept Clin Endocrinol, Oslo, Norway..
    DeFoort, C.
    INSERM, Human Nutr & Lipids 476, F-13258 Marseille, France..
    Lopez-Miranda, J.
    IMIBIC Reina Sofia Univ Hosp Univ Cordoba, Lipid & Atherosclerosis Unit, Cordoba, Spain..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Blaak, E.
    Maastricht Univ, Med Ctr, NUTRIM Sch Nutr & Translat Res Metab, NL-6200 MD Maastricht, Netherlands..
    Roche, H. M.
    UCD Conway Inst, Nutrigen Res Grp, Dublin, Ireland..
    Lovegrove, J. A.
    Univ Reading, Hugh Sinclair Unit Human Nutr, Reading RG6 6AP, Berks, England.;Univ Reading, Inst Cardiovasc & Metab Res, Reading RG6 6AP, Berks, England..
    Interactions between APOE genotype and plasma fatty acids on cardiometabolic risk markers in individuals with the Metabolic Syndrome2015In: Proceedings of the Nutrition Society, ISSN 0029-6651, E-ISSN 1475-2719, Vol. 74, no OCE5, p. E286-E286Article in journal (Other academic)
  • 27.
    Fallaize, Rosalind
    et al.
    Univ Reading, Hugh Sinclair Unit Human Nutr, Reading RG6 6AP, Berks, England.;Univ Reading, Inst Cardiovasc & Metab Res, Reading RG6 6AP, Berks, England.;Univ Hertfordshire, Sch Life & Med Sci, Coll Lane, Hatfield AL10 9AB, Herts, England..
    Carvalho-Wells, Andrew L.
    Univ Reading, Hugh Sinclair Unit Human Nutr, Reading RG6 6AP, Berks, England.;Univ Reading, Inst Cardiovasc & Metab Res, Reading RG6 6AP, Berks, England..
    Tierney, Audrey C.
    Univ Coll Dublin, Conway Inst, Nutrigen Res Grp, Dublin, Ireland..
    Marin, Carmen
    Univ Cordoba, IMIBIC, Reina Sofia Univ Hosp, Lipids & Atherosclerosis Unit, Cordoba, Spain..
    Kiec-Wilk, Beata
    Univ Med Coll, Dept Metab Dis, Krakow, Poland..
    Dembinska-Kiec, Aldona
    Jagiellonian Univ, Dept Clin Biochem, Coll Med, Krakow, Poland..
    Drevon, Christian A.
    Univ Oslo, Dept Nutr, Inst Basic Med Sci, Fac Med, Oslo, Norway..
    DeFoort, Catherine
    INSERM, Human Nutr & Lipids 476, Marseille, France..
    Lopez-Miranda, Jose
    Univ Cordoba, IMIBIC, Reina Sofia Univ Hosp, Lipids & Atherosclerosis Unit, Cordoba, Spain..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Saris, Wim H.
    MUMC, Dept Human Biol, NUTRIM Sch Nutr & Translat Res Metab, Maastricht, Netherlands..
    Blaak, Ellen E.
    MUMC, Dept Human Biol, NUTRIM Sch Nutr & Translat Res Metab, Maastricht, Netherlands..
    Roche, Helen M.
    Univ Coll Dublin, Conway Inst, Nutrigen Res Grp, Dublin, Ireland..
    Lovegrove, Julie A.
    Univ Reading, Hugh Sinclair Unit Human Nutr, Reading RG6 6AP, Berks, England.;Univ Reading, Inst Cardiovasc & Metab Res, Reading RG6 6AP, Berks, England..
    APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 6274Article in journal (Refereed)
    Abstract [en]

    Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models. At baseline E4 carriers had higher plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared with E2 carriers; and higher TC, LDL-C and apo B compared with E3/E3. Whilst elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0 was associated with insulin resistance in E4 carriers. Following FA intervention, a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo CII concentration in E2 carriers. Our novel data suggest that individuals with MetS may benefit from personalized dietary interventions based on APOE genotype.

  • 28.
    Feldreich, T
    et al.
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.; Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.; Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden .
    Urinary Osteopontin Predicts Incident Chronic Kidney Disease, while Plasma Osteopontin Predicts Cardiovascular Death in Elderly Men2017In: Cardiorenal Medicine, Vol. 7, no 3, p. 245-254Article in journal (Refereed)
    Abstract [en]

    Background and Objectives: The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied.

    Design, Setting, Participants, and Measurements: A community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM]; n = 741; mean age: 77 years) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up.

    Results: There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman. = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/ creatinine ratio, and the inflammatory markers interleukin 6 and high-sensitivity C-reactive protein (odds ratio for 1 standard deviation [SD] of urinary osteopontin, 1.42, 95% CI 1.00-2.02, p = 0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI 1.14-1.58, p < 0.001, and 1.00, 95% CI 0.79-1.26, p = 0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p < 0.002).

    Conclusions: Higher urinary osteopon-tin specifically predicts incident chronic kidney disease, while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remain to be established.

  • 29.
    Feldreich, T. Rudholm
    et al.
    Dalarna Univ, Med Sci, Falun, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Higher circulating osteopontin specifically predicts cardiovascular death while urinary osteopontin predicts kidney disease progression2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 1282-1282Article in journal (Refereed)
  • 30.
    Feldreich, T. Rudholm
    et al.
    Dalarna Univ, Med Sci, Falun, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Riserus, U
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    The association between serum cathepsin l and mortality in older adults2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 1283-1283Article in journal (Refereed)
  • 31.
    Feldreich, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. School of Health and Social Studies, Dalarna University, Falun, .
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. School of Health and Social Studies, Dalarna University, Falun, .
    The association between serum cathepsin L and mortality in older adults2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, p. 109-116Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality.

    METHODS: Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10.0 years follow-up.

    RESULTS: Higher serum cathepsin L was associated with an increased risk for cardiovascular mortality in age- and sex-adjusted models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD) increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72], p = 0.013). When merging the cohorts, these associations were independent of inflammatory markers and cardiovascular risk factors, but non-significant adjusting for kidney function. Individuals with a combination of elevated cathepsin L and increased inflammation, kidney dysfunction, or prevalent cardiovascular disease had a markedly increased risk, while no increased risk was associated with elevated cathepsin L, in the absence of these disease states.

    CONCLUSIONS: An association between higher serum cathepsin L and increased risk of cardiovascular mortality was found in two independent cohorts. Impaired kidney function appears to be an important moderator or mediator of these associations. Further studies are needed to delineate the underlying mechanisms and to evaluate whether the measurement of cathepsin L might have clinical utility.

  • 32. Garcia-Rios, Antonio
    et al.
    Delgado-Lista, Javier
    Perez-Martinez, Pablo
    Phillips, Catherine M.
    Ferguson, Jane F.
    Gjelstad, Ingrid M. F.
    Williams, Christine M.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kiec-Wilkh, Beata
    Blaak, Ellen E.
    Lairon, Denis
    Planells, Richard
    Malczewska-Malec, Malgorzata
    Defoort, Catherine
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Saris, Wim H. M.
    Lovegrove, Julie A.
    Drevon, Christian A.
    Roche, Helen M.
    Lopez-Miranda, Jose
    Genetic variations at the lipoprotein lipase gene influence plasma lipid concentrations and interact with plasma n-6 polyunsaturated fatty acids to modulate lipid metabolism2011In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 218, no 2, p. 416-422Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether seven common single nucleotide polymorphisms (SNPs) at the lipoprotein lipase (LPL) locus interact with total plasma fatty acids to modulate plasma lipid metabolism in metabolic syndrome (MetS) patients. Methods: Plasma fatty acid composition, plasma lipid concentrations and LPL SNPs were determined in 452 subjects with the MetS in the European LIPGENE human study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX Study. Results: Triglycerides (TG) were lower, and HDL higher in the carriers of rs328 and rs1059611 in the SUVIMAX cohort (all P < 0.001), and these findings showed a similar, non-significant trend in LIPGENE cohort. In this last cohort, we found a gene-fatty acids interaction, as the carriers of the minor allele displayed a lower fasting TG and triglyceride rich lipoproteins-TG (TRL-TG) concentrations only when they had n-6 polyunsaturated fatty acids below the median (all P < 0.05). Moreover, subjects carrying the minor allele for rs328 SNP and with a low level of n-6 PUFA displayed higher nonesterified fatty acid (NEFA) plasma concentrations as compared with homozygous for the major allele (P = 0.034). Interestingly, the n-6 PUFA-dependent associations between those SNPs and TG metabolism were also replicated in subjects without MetS from the SU.VI.MAX cohort. Conclusion: Two genetic variations at the LPL gene (rs328 and rs1059611) influence plasma lipid concentrations and interact with plasma n-6 PUFA to modulate lipid metabolism. The knowledge of new genetic factors together with the understanding of these gene-nutrient interactions could help to a better knowledge of the pathogenesis in the MetS. 

  • 33.
    Gidlund, Eva-Karin
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Von Eulers Vag 8, S-17177 Stockholm, Sweden..
    von Walden, Ferdinand
    Karolinska Inst, Dept Womens & Childrens Hlth, Neuropediat Unit, Stockholm, Sweden.;Astrid Lindgrens Pediat Hosp, Stockholm, Sweden..
    Venojarvi, Mika
    Univ Eastern Finland, Inst Biomed Sports & Exercise Med, Kuopio, Finland..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Heinonen, Olli J.
    Univ Turku, Paavo Nurmi Ctr, Turku, Finland.;Univ Turku, Dept Hlth & Phys Act, Turku, Finland..
    Norrbom, Jessica
    Karolinska Inst, Dept Physiol & Pharmacol, Von Eulers Vag 8, S-17177 Stockholm, Sweden..
    Sundberg, Carl Johan
    Karolinska Inst, Dept Physiol & Pharmacol, Von Eulers Vag 8, S-17177 Stockholm, Sweden..
    Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism2016In: Physiological Reports, E-ISSN 2051-817X, Vol. 4, no 23, article id e13063Article in journal (Refereed)
    Abstract [en]

    Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Whether skeletal muscle HN gene or protein expression is influenced by exercise remains unknown. In this intervention study we show, for the first time, that HN protein levels increase in human skeletal muscle following 12 weeks of resistance training in persons with prediabetes. Male subjects (n = 55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training, Nordic walking or a control group. The exercise interventions were performed three times per week for 12 weeks with progressively increased intensity during the intervention period. Biopsies from the vastus lateralis muscle and venous blood samples were taken before and after the intervention. Skeletal muscle and serum protein levels of HN were analyzed as well as skeletal muscle gene expression of the mitochondrially encoded gene MT-RNR2, containing the open reading frame for HN. To elucidate mitochondrial training adaptation, mtDNA, and nuclear DNA as well as Citrate synthase were measured. Skeletal muscle HN protein levels increased by 35% after 12 weeks of resistance training. No change in humanin protein levels was seen in serum in any of the intervention groups. There was a significant correlation between humanin levels in serum and the improvements in the 2 h glucose loading test in the resistance training group. The increase in HN protein levels in skeletal muscle after regular resistance training in prediabetic males may suggest a role for HN in the regulation of glucose metabolism. Given the preventative effect of exercise on diabetes type 2, the role of HN as a mitochondrially derived peptide and an exercise-responsive mitokine warrants further investigation.

  • 34.
    Gillberg, Linn
    et al.
    Rigshosp, Dept Endocrinol, Sect 7652,Tagensvej 20, DK-2200 Copenhagen N, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Perfilyev, Alexander
    Lund Univ, Dept Clin Sci, Epigenet & Diabet Unit, Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden..
    Brons, Charlotte
    Rigshosp, Dept Endocrinol, Sect 7652,Tagensvej 20, DK-2200 Copenhagen N, Denmark..
    Thomasen, Martin
    Rigshosp, Dept Endocrinol, Sect 7652,Tagensvej 20, DK-2200 Copenhagen N, Denmark..
    Grunnet, Louise G.
    Rigshosp, Dept Endocrinol, Sect 7652,Tagensvej 20, DK-2200 Copenhagen N, Denmark..
    Volkov, Petr
    Lund Univ, Dept Clin Sci, Epigenet & Diabet Unit, Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden..
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Dahlman, Ingrid
    Huddinge Univ Hosp, Karolinska Inst, Dept Med, S-14186 Huddinge, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Rönn, Tina
    Lund Univ, Dept Clin Sci, Epigenet & Diabet Unit, Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden..
    Nilsson, Emma
    Rigshosp, Dept Endocrinol, Sect 7652,Tagensvej 20, DK-2200 Copenhagen N, Denmark.;Lund Univ, Dept Clin Sci, Epigenet & Diabet Unit, Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden..
    Vaag, Allan
    Rigshosp, Dept Endocrinol, Sect 7652,Tagensvej 20, DK-2200 Copenhagen N, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Ling, Charlotte
    Lund Univ, Dept Clin Sci, Epigenet & Diabet Unit, Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden..
    Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 4, p. 799-812Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Individuals who had a low birthweight (LBW) are at an increased risk of insulin resistance and type 2 diabetes when exposed to high-fat overfeeding (HFO). We studied genome-wide mRNA expression and DNA methylation in subcutaneous adipose tissue (SAT) after 5 days of HFO and after a control diet in 40 young men, of whom 16 had LBW. Methods mRNA expression was analysed using Affymetrix Human Gene 1.0 ST arrays and DNA methylation using Illumina 450K BeadChip arrays. Results We found differential DNA methylation at 53 sites in SAT from LBW vs normal birthweight (NBW) men (false discovery rate < 5%), including sites in the FADS2 and CPLX1 genes previously associated with type 2 diabetes. When we used reference-free cell mixture adjustments to potentially adjust for cell composition, 4,323 sites had differential methylation in LBW vs NBW men. However, no differences in SAT gene expression levels were identified between LBW and NBW men. In the combined group of all 40 participants, 3,276 genes (16.5%) were differentially expressed in SAT after HFO (false discovery rate < 5%) and there was no difference between LBW men and controls. The most strongly upregulated genes were ELOVL6, FADS2 and NNAT; in contrast, INSR, IRS2 and the SLC27A2 fatty acid transporter showed decreased expression after HFO. Interestingly, SLC27A2 expression correlated negatively with diabetes- and obesity-related traits in a replication cohort of 142 individuals. DNA methylation at 652 CpG sites (including in CDK5, IGFBP5 and SLC2A4) was altered in SAT after overfeeding in this and in another cohort. Conclusions/interpretation Young men who had a LBW exhibit epigenetic alterations in their adipose tissue that potentially influence insulin resistance and risk of type 2 diabetes. Short-term overfeeding influences gene transcription and, to some extent, DNA methylation in adipose tissue; there was no major difference in this response between LBW and control participants.

  • 35. Gjelstad, I. M. F.
    et al.
    Haugen, F.
    Gulseth, H. L.
    Norheim, F.
    Jans, A.
    Bakke, S. S.
    Raastad, T.
    Tjonna, A. E.
    Wisloff, U.
    Blaak, E. E.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Gaster, M.
    Roche, H. M.
    Birkeland, K. I.
    Drevon, C. A.
    Expression of perilipins in human skeletal muscle in vitro and in vivo in relation to diet, exercise and energy balance2012In: Archives of Physiology and Biochemistry, ISSN 1381-3455, E-ISSN 1744-4160, Vol. 118, no 1, p. 22-30Article in journal (Refereed)
    Abstract [en]

    The perilipin proteins enclose intracellular lipid droplets. We describe the mRNA expression of the five perilipins in human skeletal muscle in relation to fatty acid supply, exercise and energy balance. We observed that all perilipins were expressed in skeletal muscle biopsies with the highest mRNA levels of perilipin 2, 4 and 5. Cultured myotubes predominantly expressed perilipin 2 and 3. In vitro, incubation of myotubes with fatty acids enhanced mRNA expression of perilipin 1, 2 and 4. In vivo, low fat diet increased mRNA levels of perilipin 3 and 4. Endurance training, but not strength training, enhanced the expression of perilipin 2 and 3. Perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity. In conclusion, all perilipins mRNAs were expressed in human skeletal muscle. Diet as well as endurance exercise modulated the expression of perilipins.

  • 36. Helal, O.
    et al.
    Defoort, C.
    Robert, S.
    Marin, C.
    Lesavre, N.
    Lopez-Miranda, J.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Basu, Samur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Lovegrove, J.
    McMonagle, J.
    Roche, H. M.
    Dignat-George, F.
    Lairon, D.
    Increased levels of microparticles originating from endothelial cells, platelets and erythrocytes in subjects with metabolic syndrome: Relationship with oxidative stress2011In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 21, no 9, p. 665-671Article in journal (Refereed)
    Abstract [en]

    Background and aims: The Metabolic Syndrome (MetS) is associated with increased cardiovascular risk. Circulating microparticles (MP) are involved in the pathogenesis of atherothrombotic disorders and are raised in individual with CVD. We measured their level and cellular origin in subjects with MetS and analyzed their associations with 1/anthropometric and biological parameters of MetS, 2/inflammation and oxidative stress markers.

    Methods and results: Eighty-eight subjects with the MetS according to the NCEP-ATPIII definition were enrolled in a bicentric study and compared to 27 healthy controls. AnnexinV-positive MP (TMP), MP derived from platelets (PMP), erythrocytes (ErMP), endothelial cells (EMP), leukocytes (LMP) and granulocytes (PNMP) were determined by flow cytometry. MetS subjects had significantly higher counts/mu l of TMP (730.6 +/- 49.7 vs 352.8 +/- 35.6), PMP (416.0 +/- 43.8 vs 250.5 +/- 23.5), ErMP (243.8 +/- 22.1 vs 73.6 +/- 19.6) and EMP (7.8 +/- 0.8 vs 4.0 +/- 1.0) compared with controls. LMP and PNMP were not statistically different between groups. Multivariate analysis demonstrated that each criterion for the MetS influenced the number of TMP. Waist girth was a significant determinant of PMP and EMP level and blood pressure was correlated with EMP level. Glycemia positively correlated with PMP level whereas dyslipidemia influenced EMP and ErMP levels. Interestingly, the oxidative stress markers, plasma glutathione peroxy-dase and urinary 8-iso-prostaglandin F(2) alpha, independently influenced TMP and PMP levels whereas inflammatory markers did not, irrespective of MP type.

    Conclusion: Increased levels of TMP, PMP, ErMP and EMP are associated with individual metabolic abnormalities of MetS and oxidative stress. Whether MP assessment may represent a marker for risk stratification or a target for pharmacological intervention deserves further investigation.

  • 37.
    Heurling, Kerstin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Moreno, Anaisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala Univ, Uppsala, Sweden..
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging. Univ Uppsala Hosp, Uppsala, Sweden..
    Eriksson, J. P.
    Univ Uppsala Hosp, Uppsala, Sweden..
    Nordeman, Patrik
    Univ Uppsala Hosp, Uppsala, Sweden..
    Sprycha, M.
    Univ Uppsala Hosp, Uppsala, Sweden..
    Wilking, H.
    Univ Uppsala Hosp, Uppsala, Sweden..
    Edner, A. Gronowski
    Univ Uppsala Hosp, Uppsala, Sweden..
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Uppsala Hosp, Uppsala, Sweden..
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Uppsala Hosp, Uppsala, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Impact of overfeeding with saturated and polyunsaturated fat on hepatic [C-11]palmitate uptake and fat content using PET-MR2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S448-S448Article in journal (Refereed)
  • 38. Hruby, Adela
    et al.
    Ngwa, Julius S.
    Renstrom, Frida
    Wojczynski, Mary K.
    Ganna, Andrea
    Hallmans, Goran
    Houston, Denise K.
    Jacques, Paul F.
    Kanoni, Stavroula
    Lehtimaki, Terho
    Lemaitre, Rozenn N.
    Manichaikul, Ani
    North, Kari E.
    Ntalla, Ioanna
    Sonestedt, Emily
    Tanaka, Toshiko
    van Rooij, Frank J. A.
    Bandinelli, Stefania
    Djousse, Luc
    Grigoriou, Efi.
    Johansson, Ingegerd
    Lohman, Kurt K.
    Pankow, James S.
    Raitakari, Olli T.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Yannakoulia, Mary
    Zillikens, M. Carola
    Hassanali, Neelam
    Liu, Yongmei
    Mozaffarian, Dariush
    Papoutsakis, Constantina
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Uitterlinden, Andre G.
    Viikari, Jorma
    Groves, Christopher J.
    Hofman, Albert
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    McCarthy, Mark I.
    Mikkila, Vera
    Mukamal, Kenneth
    Franco, Oscar H.
    Borecki, Ingrid B.
    Cupples, L. Adrienne
    Dedoussis, George V.
    Ferrucci, Luigi
    Hu, Frank B.
    Ingelsson, Erik
    Kahonen, Mika
    Kao, W. H. Linda
    Kritchevsky, Stephen B.
    Orho-Melander, Marju
    Prokopenko, Inga
    Rotter, Jerome I.
    Siscovick, David S.
    Witteman, Jacqueline C. M.
    Franks, Paul W.
    Meigs, James B.
    McKeown, Nicola M.
    Nettleton, Jennifer A.
    Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies2013In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 143, no 3, p. 345-353Article in journal (Refereed)
    Abstract [en]

    Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (In-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [beta = -0.009 mmol/L (95% CI: -0.013, -0.005), P< 0.0001] and insulin (-0.020 In-pmo/L (95% CI: -0.024, -0.017), P< 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P= 0.03) with glucose, and rs11558471 in SLC30A8and rs3740393 near CNNM2showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

  • 39. Huang, X.
    et al.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Stenvinkel, P.
    Lindholm, B.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, J. J.
    Serum fatty acid patterns, insulin sensitivity and the metabolic syndrome in individuals with chronic kidney disease2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, no 1, p. 71-83Article in journal (Refereed)
    Abstract [en]

    Objectives

    The causes of the multiple metabolic disorders of individuals with chronic kidney disease (CKD) are not fully known. We investigated the relationships between dietary fat quality, the metabolic syndrome (MetS), insulin sensitivity and inflammation in individuals with CKD.

    Subjects

    Two population-based surveys were conducted in elderly Swedish individuals (aged 70 years) with serum cystatin C-estimated glomerular filtration rate <60 mL min−1/1.73 m2: the Uppsala Longitudinal Study of Adult Men (ULSAM) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) surveys. The present population comprised 274 men and 187 subjects (63% women) from the ULSAM and PIVUS cohorts, respectively.

    Design

    Factor analyses of serum fatty acids were used to evaluate dietary fat quality. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance (IR) and, in ULSAM, also by euglycaemic clamp.

    Results

    Factor analyses generated two fatty acid patterns of (i) low linoleic acid (LA)/high saturated fatty acid (SFA) or (ii) high n-3 polyunsaturated fatty acid (n-3 PUFA) levels. In both surveys, the low LA/high SFA pattern increased the odds of having MetS [adjusted odds ratio 0.60 [95% confidence interval (CI) 0.44–0.81] and 0.45 (95% CI 0.30–0.67) per SD decrease in factor score in the ULSAM and PIVUS surveys, respectively] and was directly associated with both IR and C-reactive protein. The n-3 PUFA pattern was not consistently associated with these risk factors.

    Conclusions

    A serum fatty acid pattern reflecting low LA and high SFA was strongly associated with MetS, IR and inflammation in two independent surveys of elderly individuals with CKD. At present, there are no specific dietary guidelines for individuals with CKD; however, these findings indirectly support current recommendations to replace SFAs with PUFAs from vegetable oils.

  • 40. Huang, X.
    et al.
    Stenvinkel, P.
    Qureshi, A. R.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Barany, P.
    Heimburger, O.
    Lindholm, B.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, J. J.
    Clinical determinants and mortality predictability of stearoyl-CoA desaturase-1 activity indices in dialysis patients2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 273, no 3, p. 263-272Article in journal (Refereed)
    Abstract [en]

    Huang X, Stenvinkel P, Qureshi AR, Cederholm T, Barany P, Heimburger O, Lindholm B, Riserus U, Carrero JJ (Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm; and Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden). Clinical determinants andmortality predictability of stearoyl-CoA desaturase-1 activity indices in dialysis patients. J InternMed 2013; 273: 263-272. Background Stearoyl-CoA desaturase-1 (SCD-1) converts dietary saturated fatty acids to monounsaturated fatty acids. Elevated SCD-1 activity thus signifies impaired fatty acid metabolism and excess saturated fat intake. In the general population, increased SCD-1 activity is associated with cardiovascular disease and mortality. The determinants and implications of SCD-1 activity in dialysis patients are unknown. Subjects A total of 222 dialysis patients (39% women) with prospective follow-up, median age of 57years and an average of 12months of dialysis. Design Fatty acid compositions in plasma phospholipids and free fatty acids (FFAs) were assessed by gasliquid chromatography. SCD-1 activity indices were calculated as the product-to-precursor fatty acid ratio (palmitoleic acid/palmitic acid) in each fraction to reflect SCD-1 activities in the liver and adipose tissue. Results Median hepatic and adipose tissue SCD-1 activity indices were 0.016 and 0.150, respectively. In multivariate analyses, SCD-1 was positively associated with age, female sex and serum interleukin-6 level. During 18.4 (interquartile range 5.537.3) months of follow-up, there were 61 deaths and 115 kidney transplants. The cut-off level for high SCD-1 indices was determined by receiver operating characteristic curve analyses. In fully adjusted competing risk models, patients with high SCD-1 indices in both phospholipids and FFAs had more than twofold increased mortality risk before kidney transplantation [hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.284.11 and HR 2.36, 95% CI 1.384.03, respectively], compared with patients with low SCD-1 indices. Conclusions Both hepatic and adipose tissue SCD-1 activity indices independently predict mortality in dialysis patients. Further studies are warranted to determine whether reducing SCD-1 activity by dietary intervention (limiting saturated fat) could improve survival in dialysis patients.

  • 41. Huang, Xiaoyan
    et al.
    Juan Jimenez-Moleon, Jose
    Lindholm, Bengt
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Mediterranean Diet, Kidney Function, and Mortality in Men with CKD2013In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 8, no 9, p. 1548-1555Article in journal (Refereed)
    Abstract [en]

    Background and objectivesAdherence to a Mediterranean diet may link to a better preserved kidney function in the community as well as a favorable cardiometabolic profile and reduced mortality risk in individuals with manifest CKD.Design, setting, participants, & measurementsDietary habits were determined by 7-day dietary records in a population-based cohort of 1110 Swedish men (age 70 years) from 1991 to 1995, 506 of whom were considered to have CKD because of a GFR<60 ml/min per 1.73 m(2). A Mediterranean Diet Score was calculated, and participants were categorized as having low, medium, or high adherence. Adequate dietary reporters were identified with Goldberg cutoffs (n=597). Deaths were registered during a median follow-up of 9.9 years.ResultsCompared with low adherents, medium and high adherents were 23% and 42% less likely to have CKD, respectively (adjusted odds ratio [95% confidence interval]=0.77 [0.57 to 1.05] and 0.58 [0.38 to 0.87], respectively, P for trend=0.04). Among those individuals with CKD, phosphate intake and net endogenous acid production were progressively lower across increasing adherence groups. No differences were observed regarding other cardiometabolic risk factors across adherence groups. As many as 168 (33%) CKD individuals died during follow-up. Compared with low adherents, proportional hazards regression associated medium and high adherents to a 25% and 23% lower mortality risk, respectively (adjusted hazard ratio [95% confidence interval]=0.75 [0.52 to 1.06] and 0.77 [0.44 to 1.36], respectively, P for trend=0.10). Sensitivity analyses showed significant and stronger associations when only adequate dietary reporters were considered.ConclusionsAdherence to a Mediterranean dietary pattern is associated with lower likelihood of CKD in elderly men. A greater adherence to this diet independently predicted survival in those patients with manifest CKD. Clinical trials are warranted to test the hypothesis that following such a diet could improve outcomes (independent of other healthy lifestyles) in CKD patients.

  • 42. Huang, Xiaoyan
    et al.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesús
    Serum and adipose tissue fatty acid composition as biomarkers of habitual dietary fat intake in elderly men with chronic kidney disease2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no 1, p. 128-136Article in journal (Refereed)
    Abstract [en]

    Background

    Fatty acid (FA) composition in serum cholesterol esters (CE) and adipose tissue (AT) reflect the long-term FA intake in the general population. Because both dietary intake and FA biomarkers associate with renal function, our aim was to identify which CE and AT FAs are useful biomarkers of habitual FA intake in individuals with chronic kidney disease (CKD).

    Methods

    Cross-sectional analysis was performed in 506 men (aged 70 years) with a glomerular filtration rate (GFR) of <60 mL/min per 1.73 m(2) from the Uppsala Longitudinal Study of Adult Men cohort. Dietary habits were evaluated with a 7-day dietary record. FA compositions in CE and AT were analyzed by gas-liquid chromatography in two random subsamples of 248 and 318 individuals, respectively.

    Results

    Both CE and AT linoleic acid and docosahexaenoic acid (DHA) were strongly associated with their corresponding intake, after adjustments for non-dietary factors. The proportions of eicosapentaenoic acid (EPA) and palmitic acid in CE and AT moderately correlated with dietary intake, whereas correlations of other FAs were weaker or absent. Proportions of EPA and DHA in CE and AT were positively associated with the total energy-adjusted fish intake. Results were confirmed in adequate reporters as identified by the Goldberg cutoff method. These relationships held constant, regardless of a GFR above or below 45 mL/min per 1.73 m(2) or the prevalence of microalbuminuria.

    Conclusions

    Proportions of EPA, DHA, palmitic and linoleic acid in serum CE and AT are good indicators of their dietary intake in men with CKD. They can be considered valid biomarkers for epidemiological studies and assessment of compliance.

  • 43. Huang, Xiaoyan
    et al.
    Stenvinkel, Peter
    Qureshi, Abdul Rashid
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Barany, Peter
    Heimburger, Olof
    Lindholm, Bengt
    Carrero, Juan Jesus
    Essential polyunsaturated fatty acids, inflammation and mortality in dialysis patients2012In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 27, no 9, p. 3615-3620Article in journal (Refereed)
    Abstract [en]

    Background. Polyunsaturated fatty acids (PUFA) are essential nutrients with anti-inflammatory and cardioprotective properties. We investigated the association of essential dietary PUFA intake, reflected by plasma fatty acid composition, with inflammation and mortality in dialysis patients.

    Methods. We recruited 222 Swedish dialysis subjects (39% women) with median age of 57 years and average 12 months of dialysis vintage. Plasma phospholipid PUFA were assessed by gas-liquid chromatography. Overall mortality was assessed after 18.4 (10th-90th percentiles: 2.3-60) months of follow-up.

    Results. Linoleic acid (LA), Mead acid (MA), alpha-linolenic acid (ALA) and long-chain n-3 PUFA (LC n-3; the sum of eicosapentaenoic, docosapentaenoic and docosahexaenoic acids) represented 19.7, 0.26, 0.26 and 7.64% of all fatty acids in plasma, respectively. This may reflect an adequate n-3 PUFA intake. LA was negatively (beta = -0.21, P = 0.004) but MA positively (beta = 0.25, P < 0.001) associated with interleukin (IL)-6 in multivariate analyses. Neither ALA nor LC n-3 were independently associated with IL-6. During follow-up, 61 deaths and 115 kidney transplants occurred. Fully adjusted competing risk models showed that every percent increase in the proportion of plasma LA was associated with 12% reduction in mortality risk before transplantation (hazard ratio 0.88, 95% confidence interval 0.79-0.99). MA was directly associated with mortality. Neither ALA nor LC n-3 predicted outcome.

    Conclusions. The proportion of plasma phospholipid LA is inversely associated with IL-6 and all-cause mortality in Swedish dialysis patients. We raise the hypothesis that dialysis patients could benefit from increased intake of vegetable oils, the primary source of LA in the Western-type diet.

  • 44.
    Iggman, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Beckman, Lena
    Rudling, Mats
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Role of Dietary Fats in Modulating Cardiometabolic Risk During Moderate Weight Gain: A Randomized Double-Blind Overfeeding Trial (LIPOGAIN Study)2014In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 3, no 5, article id e001095Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study.

    METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001).

    CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA.

    CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

  • 45.
    Iggman, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. School of Health and Social Studies, Dalarna University.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Association of Adipose Tissue Fatty Acids With Cardiovascular and All-Cause Mortality in Elderly Men2016In: JAMA cardiology, ISSN 2380-6591, Vol. 1, no 7, p. 745-753Article in journal (Refereed)
    Abstract [en]

    Importance: The major polyunsaturated fatty acids in adipose tissue objectively reflect long-term dietary intake, and may provide more reliable information than would self-reported intake. Whether adipose tissue fatty acids predict cardiovascular and all-cause mortality needs investigation.

    Objective: To investigate associations between adipose tissue fatty acids and cardiovascular and overall mortality in a cohort of elderly men.

    Design, Setting, and Participants: We hypothesized that polyunsaturated fatty acids reflecting dietary intake, are inversely associated with cardiovascular and all-cause mortality. In the Swedish cohort study Uppsala Longitudinal Cohort of Adult Men, buttock fatty acid composition was analyzed by gas-liquid chromatography in 1992 to 1993 and 2008. The study participants were followed during 11 311 person-years, between 1991 and 2011 (median follow-up, 14.8 years). In this community-based study that took place from 1970 to 1973, all men born in 1920 to 1924 in Uppsala, Sweden, were invited and 2322 (82%) were included (at age 50 years). At the reinvestigation at age 71 years, 1221 (73%) of the 1681 invited men participated. Adipose tissue biopsy specimens were taken in a subsample of 853 men. There was no loss to follow-up.

    Exposures: Adipose tissue proportions of 4 polyunsaturated fatty acids that were considered to mainly reflect dietary intake (linoleic acid, 18:2n-6; α-linolenic acid, 18:3n-3; eicosapentaenoic acid, 20:5n-3; and docosahexaenoic acid, 22:6n-3) comprised primary analyses, and all other available fatty acids were secondary analyses.

    Main Outcomes and Measures: Hazard ratios (HRs) for cardiovascular and all-cause mortality using Cox proportional hazards regression analyses, performed in 2015.

    Results: Among the 853 Swedish men, there were 605 deaths, of which 251 were cardiovascular deaths. After adjusting for risk factors, none of the 4 primary fatty acids were associated with cardiovascular mortality (HR, 0.92-1.05 for each standard deviation increase; P ≥ .27). Linoleic acid was inversely associated with all-cause mortality (HR, 0.90; 95% CI, 0.82-0.98; P = .02) and directly associated with intake (P < .001). In secondary analyses, palmitoleic acid, 16:1n-7 (HR, 1.11; 95% CI, 1.02-1.21; P = .02) was associated with higher all-cause mortality, whereas heptadecanoic acid, 17:0, tended to be associated with lower all-cause mortality (HR, 0.89; 95% CI, 0.79-1.00; P = .05). Arachidonic:linoleic acid ratio was associated with both cardiovascular (HR, 1.15; 95% CI, 1.05-1.31; P = .04) and all-cause (HR, 1.13; 95% CI, 1.04-1.23; P = .005) mortality.

    Conclusions and Relevance: Adipose tissue linoleic acid was inversely associated with all-cause mortality in elderly men, although not significantly with cardiovascular mortality.

  • 46.
    Ingelsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Frystyk, Jan
    Flyvbjerg, Allan
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Adiponectin and risk of congestive heart failure2006In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 295, no 15, p. 1772-1774Article in journal (Refereed)
  • 47.
    Ingelsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men2007In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, no 14, p. 1739-1745Article in journal (Refereed)
    Abstract [en]

    Aims To investigate associations of urinary albumin excretion rate (UAER) and heart failure (HF) incidence in a community-based sample.

    Methods and results In a prospective study of 70-year-old men free from HF at baseline (n = 1106), UAER (from timed overnight samples) was analysed with established risk factors for HF [acute MI before baseline, acute MI during follow-up (modelled as a time-dependent covariate), hypertension, diabetes, left ventricular hypertrophy, smoking, body mass index, and glomerular filtration rate] and more recently described risk factors [high-sensitive C-reactive protein and insulin sensitivity (clamp glucose disposal rate)] as predictors of HF incidence.

    Ninety-eight participants developed HF during a median follow-up of 9.0 years. In Cox proportional hazards models adjusted for established and novel risk factors for HF, a 1 SD increase in log UAER increased the risk of HF in individuals without anti-hypertensive treatment (hazard ratio 1.49; 95% CI 1.13–1.98; P = 0.005). Furthermore, UAER remained an independent predictor of HF, also in participants without diabetes at baseline or myocardial infarction at baseline or during follow-up. There were no significant associations between UAER and HF incidence in individuals with anti-hypertensive treatment.

    Conclusion Our observations support the notion that low-grade albuminuria is a marker for subclinical cardiovascular damage that predisposes to future HF in the community.

  • 48.
    Ingelsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Relative importance and conjoint effects of obesity and physical inactivity for the development of insulin resistance2009In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, no 1, p. 28-33Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity and physical inactivity are related to the development of insulin resistance, but their relative importance and conjoint effects are unclear. METHODS: We related body mass index (BMI) and self-reported leisure-time physical activity (PA) at the age of 50 years to insulin sensitivity measured with euglycemic insulin clamp technique and the presence of metabolic syndrome (MetS) at a subsequent examination, 20 years later, in 862 men free from diabetes and MetS at baseline. RESULTS: In a multivariable model including BMI, PA, homeostasis model assessment insulin resistance index, erythrocyte sedimentation rate, and all components of MetS at baseline, both BMI (beta, -0.19 mg/kg bodyweight/min per 1 kg/m; P<0.0001) and PA (adjusted least square means, 5.1, 5.2, 5.4, and 6.2 mg/kg bodyweight/min in individuals with sedentary, moderate, regular, and athletic PA, respectively; P=0.0035) were significant predictors of insulin sensitivity at age 70. When categorizing individuals into four groups by BMI and PA at baseline, insulin sensitivity at the age of 70 years decreased significantly over the following categories: multivariable-adjusted least square means, 5.8 (low BMI/high PA); 5.6 (low BMI/low PA); 5.1 (high BMI/high PA); and 4.6 (high BMI/low PA) mg/kg bodyweight/min, respectively; P value of less than 0.0001. CONCLUSION: In our community-based sample of middle-aged men, BMI and PA were independent predictors of insulin resistance after 20 years of follow-up. Our results imply that obesity and physical inactivity may increase insulin resistance and metabolic risk by partly independent pathways, and emphasize the importance of strategies that address both obesity and physical inactivity to achieve increased public health.

  • 49.
    Jacobsson, Josefin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Moschonis, G
    Koumpitski, A
    Chrousos, G P
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Marcus, C
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Genetic variants near the MGAT1 gene are associated with body weight, BMI and fatty acid metabolism among adults and children2012In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, no 1, p. 119-129Article in journal (Refereed)
    Abstract [en]

    Objective: Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-β-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men.

    Design: Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children.

    Results: Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95% confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95% CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95% CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95% CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95%CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95% CI:0.093-0.373, P=0.001) and 0.147 (95% CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038).

    Conclusion: Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity.

  • 50. Jans, A.
    et al.
    Van Hees, A. M. J.
    Gjelstad, I. M. F.
    Sparks, L. M.
    Tierney, A. C.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Drevon, C. A.
    Schrauwen, P.
    Roche, H. M.
    Blaak, E. E.
    Impact of dietary fat quantity and quality on skeletal muscle fatty acid metabolism in subjects with the metabolic syndrome2012In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 61, no 11, p. 1554-1565Article in journal (Refereed)
    Abstract [en]

    Insulin resistance is characterized by disturbances in lipid metabolism in skeletal muscle. Our aim was to investigate whether gene expression and fatty acid (FA) profile of skeletal muscle lipids are affected by diets differing in fat quantity and quality in subjects with the metabolic syndrome (MetS) and varying degrees of insulin sensitivity. 84 subjects (age 57.3 ± 0.9 y, BMI 30.9 ± 0.4 kg/m 2, 42 M/42 F) were randomly assigned to one of four iso-energetic diets: high-SFA (HSFA); high-MUFA (HMUFA) or two low-fat, high-complex carbohydrate diets, supplemented with 1.24 g/day of long-chain n-3 PUFA (LFHCCn-3) or control oil (LFHCC) for 12 weeks. In a subgroup of men (n = 26), muscle TAG, DAG, FFA and phospholipid contents were determined including their fractional synthetic rate (FSR) and FA composition at fasting and 4 h after consumption of a high-fat mixed-meal, both pre- and post-intervention. Genes involved in lipogenesis were downregulated after HMUFA (mean fold change - 1.3) and after LFHCCn-3 (fold change - 1.7) in insulin resistant subjects (&lt; median of (S I)), whereas in insulin sensitive subjects (&gt; median of insulin sensitivity) the opposite effect was shown (fold change + 1.6 for both diets). HMUFA diet tended to decrease FSR in TAG (P =.055) and DAG (P =.066), whereas the LFHCCn-3 diet reduced TAG content (P =.032). In conclusion, HMUFA and LFHCCn-3 diets reduced the expression of the lipogenic genes in skeletal muscle of insulin resistant subjects, whilst HMUFA reduced the fractional synthesis rate of DAG and TAG and LFHCC n-3 the TAG content. Our data indicate that these diets may reduce muscle fat accumulation by affecting the balance between FA synthesis, storage and oxidation.

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