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Ulven, S. M., Holven, K. B., Rundblad, A., Myhrstad, M. C. W., Leder, L., Dahlman, I., . . . Kolehmainen, M. (2019). An Isocaloric Nordic Diet Modulates RELA and TNFRSF1A Gene Expression in Peripheral Blood Mononuclear Cells in Individuals with Metabolic Syndrome-A SYSDIET Sub-Study. Nutrients, 11(12), Article ID 2932.
Open this publication in new window or tab >>An Isocaloric Nordic Diet Modulates RELA and TNFRSF1A Gene Expression in Peripheral Blood Mononuclear Cells in Individuals with Metabolic Syndrome-A SYSDIET Sub-Study
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2019 (English)In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 12, article id 2932Article in journal (Refereed) Published
Abstract [en]

A healthy dietary pattern is associated with a lower risk of metabolic syndrome (MetS) and reduced inflammation. To explore this at the molecular level, we investigated the effect of a Nordic diet (ND) on changes in the gene expression profiles of inflammatory and lipid-related genes in peripheral blood mononuclear cells (PBMCs) of individuals with MetS. We hypothesized that the intake of an ND compared to a control diet (CD) would alter the expression of inflammatory genes and genes involved in lipid metabolism. The individuals with MetS underwent an 18/24-week randomized intervention to compare a ND with a CD. Eighty-eight participants (66% women) were included in this sub-study of the larger SYSDIET study. Fasting PBMCs were collected before and after the intervention and changes in gene expression levels were measured using TaqMan Array Micro Fluidic Cards. Forty-eight pre-determined inflammatory and lipid related gene transcripts were analyzed. The expression level of the gene tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) was down-regulated (p = 0.004), whereas the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) subunit, RELA proto-oncogene, was up-regulated (p = 0.016) in the ND group compared to the CD group. In conclusion, intake of an ND in individuals with the MetS may affect immune function.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
metabolic syndrome, randomized controlled dietary intervention, gene expression, peripheral blood mononuclear cells, inflammation
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-406064 (URN)10.3390/nu11122932 (DOI)000506917800094 ()31816875 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung FoundationNordForsk, 070014Academy of FinlandSwedish Diabetes Association
Available from: 2020-03-04 Created: 2020-03-04 Last updated: 2020-03-04Bibliographically approved
Brunner, F. J., Waldeyer, C., Ojeda, F., Salomaa, V., Kee, F., Sans, S., . . . Ikram, M. K. (2019). Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium. The Lancet, 394(10215), 2173-2183
Open this publication in new window or tab >>Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium
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2019 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10215, p. 2173-2183Article in journal (Refereed) Published
Abstract [en]

Background The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. Methods In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. Findings Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48.7%] women; median age 51.0 years [IQR 40.7-59.7]). 199 415 individuals were included in the derivation cohort (91 786 [48.4%] women) and 199 431 (92 269 [49.1%] women) in the validation cohort. During a maximum follow-up of 43.6 years (median 13.5 years, IQR 7.0-20.1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease eventrates for increasing non-HDL cholesterol categories (from 7.7% for non-HDL cholesterol <2.6 mmol/L to 33.7% for >= 5.7 mmol/L in women and from 12.8% to 43.6% in men; p<0.0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2.6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1.1, 95% CI 1.0-1.3 for nonHDL cholesterol 2.6 to <3.7 mmol/L to 1.9, 1.6-2.2 for >= 5.7 mmol/L in women and from 1.1, 1.0-1.3 to 2.3, 2.0-2.5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. Interpretation Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2019
National Category
Cardiac and Cardiovascular Systems Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-401185 (URN)10.1016/S0140-6736(19)32519-X (DOI)000502546300027 ()31810609 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, HEALTH-F2-2011-278913EU, FP7, Seventh Framework Programme, HEALTH-F3-2010-242244
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-01-07Bibliographically approved
Marklund, M., Wu, J. H. Y., Imamura, F., Del Gobbo, L. C., Fretts, A., de Goede, J., . . . Risérus, U. (2019). Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies. Circulation, 139(21), 2422-2436
Open this publication in new window or tab >>Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 21, p. 2422-2436Article in journal (Refereed) Published
Abstract [en]

Background:

Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

Methods:

We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

Results:

In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

Conclusions:

In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Keywords
arachidonic acid, biomarkers, cardiovascular diseases, diet, epidemiology, linoleic acid, primary prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-387592 (URN)10.1161/CIRCULATIONAHA.118.038908 (DOI)000469018300011 ()30971107 (PubMedID)
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved
Gulseth, H. L., Gjelstad, I. M. F., Tiereny, A. C., McCarthy, D., Lovegrove, J. A., Defoort, C., . . . Birkeland, K. I. (2019). Effects of dietary fat on insulin secretion in subjects with the metabolic syndrome. European Journal of Endocrinology, 180(5), 321-328
Open this publication in new window or tab >>Effects of dietary fat on insulin secretion in subjects with the metabolic syndrome
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2019 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 180, no 5, p. 321-328Article in journal (Refereed) Published
Abstract [en]

Objective: Impaired insulin secretion and action contribute to the development of type 2 diabetes. Dietary fat modification may improve insulin sensitivity, whereas the effect on insulin secretion is unclear. We investigated the effect of dietary fat modification on insulin secretion in subjects with the metabolic syndrome.

Design: In a 12-week pan-European parallel, randomized controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to four isoenergetic diets: high-fat diets rich in saturated fat (HSFA) or monounsaturated fat (HMUFA) or low-fat, high-complex carbohydrate diets with (LFHCC n-3) or without (LFHCC control) 1.2 g/day of n-3 PUFA supplementation. Insulin secretion was estimated as acute insulin response to glucose (AIRg) and disposition index (DI), modeled from an intravenous glucose tolerance test.

Results: There were no overall effect of the dietary intervention on AIRg and DI in the total cohort, in neither the highfat nor LFHCC groups. We observed significant diet*fasting glucose category interactions for AIRg (P = 0.021) and DI (P = 0.001) in the high-fat groups. In subjects with normal fasting glucose and preserved first phase insulin secretion, the HMUFA diet increased, whereas the HSFA diet reduced AIRg (P = 0.015) and DI (P = 0.010).

Conclusions: The effects of dietary fat modification on insulin secretion were minor, and only evident in normoglycemic subjects. In this case, the HMUFA diet improved AIRg and DI, as compared to the HSFA diet.

Place, publisher, year, edition, pages
BIOSCIENTIFICA LTD, 2019
National Category
Nutrition and Dietetics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-382818 (URN)10.1530/EJE-19-0022 (DOI)000464997600007 ()30893645 (PubMedID)
Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-05-06Bibliographically approved
Johansson, H.-E., Edholm, D., Kullberg, J., Rosqvist, F., Rudling, M., Straniero, S., . . . Risérus, U. (2019). Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements. Nutrition & Diabetes, 9(1), Article ID 34.
Open this publication in new window or tab >>Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements
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2019 (English)In: Nutrition & Diabetes, ISSN 2044-4052, E-ISSN 2044-4052, Vol. 9, no 1, article id 34Article in journal (Refereed) Published
Abstract [en]

Energy restriction reduces liver fat, improves hepatic insulin resistance and lipid metabolism. However, temporal data in which these metabolic improvements occur and their interplay is incomplete. By performing repeated MRI scans and blood analysis at day 0, 3, 7, 14 and 28 the temporal changes in liver fat and related metabolic factors were assessed at five times during a low-calorie diet (LCD, 800-1100 kcal/day) in ten obese non-diabetic women (BMI 41.7 ± 2.6 kg/m2) whereof 6 had NAFLD. Mean weight loss was 7.4 ± 1.2 kg (0.7 kg/day) and liver fat decreased by 51 ± 16%, resulting in only three subjects having NAFLD at day 28. Marked alteration of insulin, NEFA, ALT and 3-hydroxybuturate was evident 3 days after commencing LCD, whereas liver fat showed a moderate but a linear reduction across the 28 days. Other circulating-liver fat markers (e.g. triglycerides, adiponectin, stearoyl-CoA desaturase-1 index, fibroblast growth factor 21) demonstrated modest and variable changes. Marked elevations of NEFA, 3-hydroxybuturate and ALT concentrations occurred until day 14, likely reflecting increased tissue lipolysis, fat oxidation and upregulated hepatic fatty acid oxidation. In summary, these results suggest linear reduction in liver fat, time-specific changes in metabolic markers and insulin resistance in response to energy restriction.

National Category
Endocrinology and Diabetes Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-397554 (URN)10.1038/s41387-019-0100-2 (DOI)000497994200004 ()31685793 (PubMedID)
Available from: 2019-11-21 Created: 2019-11-21 Last updated: 2019-12-18Bibliographically approved
Myhrstad, M. C. W., de Mello, V. D., Dahlman, I., Kolehmainen, M., Paananen, J., Rundblad, A., . . . Ulven, S. M. (2019). Healthy Nordic Diet Modulates the Expression of Genes Related to Mitochondrial Function and Immune Response in Peripheral Blood Mononuclear Cells from Subjects with Metabolic Syndrome-A SYSDIET Sub-Study. Molecular Nutrition & Food Research, 63(13), Article ID 1801405.
Open this publication in new window or tab >>Healthy Nordic Diet Modulates the Expression of Genes Related to Mitochondrial Function and Immune Response in Peripheral Blood Mononuclear Cells from Subjects with Metabolic Syndrome-A SYSDIET Sub-Study
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2019 (English)In: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 63, no 13, article id 1801405Article in journal (Refereed) Published
Abstract [en]

Scope To explore the effect of a healthy Nordic diet on the global transcriptome profile in peripheral blood mononuclear cells (PBMCs) of subjects with metabolic syndrome. Methods and results Subjects with metabolic syndrome undergo a 18/24 week randomized intervention study comparing an isocaloric healthy Nordic diet with an average habitual Nordic diet served as control (SYSDIET study). Altogether, 68 participants are included. PBMCs are obtained before and after intervention and total RNA is subjected to global transcriptome analysis. 1302 probe sets are differentially expressed between the diet groups (p-value < 0.05). Twenty-five of these are significantly regulated (FDR q-value < 0.25) and are mainly involved in mitochondrial function, cell growth, and cell adhesion. The list of 1302 regulated probe sets is subjected to functional analyses. Pathways and processes involved in the mitochondrial electron transport chain, immune response, and cell cycle are downregulated in the healthy Nordic diet group. In addition, gene transcripts with common motifs for 42 transcription factors, including NFR1, NFR2, and NF-kappa B, are downregulated in the healthy Nordic diet group. Conclusion These results suggest that benefits of a healthy diet may be mediated by improved mitochondrial function and reduced inflammation.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
gene-expression, healthy Nordic diet, metabolic syndrome, peripheral blood mononuclear cells, transcriptome
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-390915 (URN)10.1002/mnfr.201801405 (DOI)000473667000001 ()30964598 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung FoundationNordForsk, 070014Swedish Diabetes Association
Available from: 2019-08-15 Created: 2019-08-15 Last updated: 2019-08-15Bibliographically approved
Diamanti, K., Cavalli, M., Pan, G., Pereira, M. J., Kumar, C., Skrtic, S., . . . Wadelius, C. (2019). Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes. Scientific Reports, 9, Article ID 9653.
Open this publication in new window or tab >>Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9653Article in journal (Refereed) Published
Abstract [en]

Type 2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from 43 multi-organ donors. The intra-individual analysis was assessed across five key metabolic tissues (serum, visceral adipose tissue, liver, pancreatic islets and skeletal muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. In diabetes cases, carnitines were significantly higher in liver, while lysophosphatidylcholines were significantly lower in muscle and serum. We tracked the primary tissue of origin for multiple metabolites whose alterations were reflected in serum. An investigation of three major stages spanning from controls, to pre-diabetes and to overt T2D indicated that a subset of lysophosphatidylcholines was significantly lower in the muscle of pre-diabetes subjects. Moreover, glycodeoxycholic acid was significantly higher in liver of pre-diabetes subjects while additional increase in T2D was insignificant. We confirmed many previously reported findings and substantially expanded on them with altered markers for early and overt T2D. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-391017 (URN)10.1038/s41598-019-45906-5 (DOI)000474222900010 ()31273253 (PubMedID)
Funder
AstraZenecaSwedish Research Council FormaseSSENCE - An eScience CollaborationSwedish Diabetes AssociationErnfors Foundation
Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-09-22Bibliographically approved
Tan, X., Cedernaes, J., Risérus, U. & Benedict, C. (2019). Lack of association between self-reported insomnia symptoms and clamp-derived insulin sensitivity in elderly men. Psychoneuroendocrinology, 102, 256-260
Open this publication in new window or tab >>Lack of association between self-reported insomnia symptoms and clamp-derived insulin sensitivity in elderly men
2019 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 102, p. 256-260Article in journal (Refereed) Published
Abstract [en]

Insomnia-related sleep disruptions, such as short and disturbed sleep, have been tied to systemic insulin resistance in young adult populations. We therefore sought to confirm these findings in a cohort of elderly men. To this aim, we utilized variables from 980 men who participated in the investigation at age 70 of the Uppsala Longitudinal Study of Adult Men. Self-reported insomnia symptoms were assessed by questions about difficulty initiating sleep, early final awakening, and regular use of hypnotics. All participants also underwent the gold standard hyperinsulinemic-euglycemic clamp technique to assess the insulin sensitivity index (M/I). Finally, fasting blood was collected to measure free fatty acids (FFAs) and adiponectin. Differences in blood parameters between men with and those without insomnia were determined by ANCOVA, and were adjusted for lifestyle and cardio-metabolic risk factors. Our analysis yielded no differences in M/I, FFAs, and adiponectin between men with and those without insomnia symptoms. Analyses in non-diabetic and diabetic subsamples confirmed these negative findings. Our cross-sectional results therefore suggest that insomnia symptoms may have a minimal effect, if any, on measures of insulin sensitivity in elderly men. Given the observational design of our study, future studies are needed to determine whether experimental sleep manipulations influence systemic insulin sensitivity in elderly humans, as has previously been shown in young adult populations.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2019
Keywords
Male cohort, Insomnia symptoms, Clamp-derived insulin sensitivity, Adiponectin, Free fatty acids
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-382522 (URN)10.1016/j.psyneuen.2018.12.227 (DOI)000462800900032 ()30594818 (PubMedID)
Funder
Swedish Research Council, 2015-03100Novo Nordisk, NNF14OC0009349The Swedish Brain FoundationÅke Wiberg Foundation, M17-0088Fredrik och Ingrid Thurings Stiftelse, 2017-00313
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved
Rosqvist, F., Kullberg, J., Ståhlman, M., Cedernaes, J., Heurling, K., Johansson, H.-E., . . . Risérus, U. (2019). Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat: a randomized trial. Journal of Clinical Endocrinology and Metabolism, 104(12), 6207-6219
Open this publication in new window or tab >>Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat: a randomized trial
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2019 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 12, p. 6207-6219Article in journal (Refereed) Published
Abstract [en]

CONTEXT: Saturated fat (SFA) versus polyunsaturated fat (PUFA) may promote non-alcoholic fatty liver disease (NAFLD) by yet unclear mechanisms.

OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.

DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.

SETTING: General community.Participants: n=61 overweight or obese men and women.

INTERVENTION: Muffins high in either palm (SFA)- or sunflower oil (PUFA) were added to the habitual diet.

MAIN OUTCOME MEASURE: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.

RESULTS: By design, body weight gain was similar in SFA (2.31±1.38 kg) and PUFA (2.01±1.90 kg) groups, P=0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat or total body fat compared with PUFA. SFA consistently increased, while PUFA reduced circulating ceramides; changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.

CONCLUSIONS: Saturated fat markedly induces liver fat and serum ceramides whereas dietary polyunsaturated fat prevent liver fat accumulation, reduce ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Nutrition and Dietetics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-391140 (URN)10.1210/jc.2019-00160 (DOI)31369090 (PubMedID)
Funder
Swedish Research Council, K2015-54X-22081-04-3Swedish Research Council, 2016-01040Swedish Research Council, 2015-02781Swedish Heart Lung Foundation, 20160491Stockholm County Council, ALF 20150447Ernfors FoundationSwedish Nutrition Foundation (SNF)EXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2020-03-20Bibliographically approved
Tuomainen, M., Kärkkäinen, O., Leppänen, J., Auriola, S., Lehtonen, M., Savolainen, M. J., . . . Hanhineva, K. (2019). Quantitative assessment of betainized compounds and associations with dietary and metabolic biomarkers in the randomized study of the healthy Nordic diet (SYSDIET). American Journal of Clinical Nutrition, 110(5), 1108-1118
Open this publication in new window or tab >>Quantitative assessment of betainized compounds and associations with dietary and metabolic biomarkers in the randomized study of the healthy Nordic diet (SYSDIET)
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2019 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 110, no 5, p. 1108-1118Article in journal (Refereed) Published
Abstract [en]

Background: Recently, a group of betainized compounds have been suggested to play a role in health effects in relation to a whole-grain-rich diet.

Objectives: The aims of this study were to develop a quantitative mass spectrometric method for selected betainized compounds in human plasma, and to investigate their association with nutrient intake and measures of metabolic health in participants of the SYSDIET study.

Methods: The SYSDIET study was a controlled randomized intervention including individuals with metabolic syndrome, where the healthy Nordic diet (HND) group increased intakes of whole grains, canola oil, berries, and fish, whereas the control diet (CD) group consumed low-fiber cereal products, milk fat, and restricted amounts of fish and berries. A quantitative LC combined with triple quadrupole MS method for betainized compounds was developed and applied to fasting plasma samples from baseline (week 0) and the end of the intervention (week 18 or 24). Concentrations of betainized compounds were correlated with intakes of selected nutrients and fiber and measures of metabolic health.

Results: Pipecolic acid betaine (PAB) concentrations were significantly higher in the HND group than in the CD group (P = 0.00032) at the end of the intervention and correlated directly (P < 0.0001) with intakes of dietary fiber (r = 0.376) and a biomarker related to whole-grain rye intake, namely the ratio of alkylresorcinol C17:0 to C21:0 (r = 0.442). PAB was associated inversely with fasting plasma insulin consistently at the beginning and at the end of the intervention (P < 0.001, r = -0.300; P < 0.01, r = -0.250, respectively), as well as IL-1 receptor antagonist (P < 0.01, r = -0.232 at the beginning; P < 0.01, r = -0.236 at the end) and serum LDL/HDL cholesterol (P < 0.01, r = -0.239 at the beginning; P < 0.01, r = -0.241 at the end).

Conclusions: Among adults with the metabolic syndrome, PAB plasma concentrations were associated with fasting insulin, inflammation, and lipids and were significantly increased with adoption of the HND. Further studies are needed to clarify the biological functions of betainized compounds.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2019
Keywords
betainized compounds, fiber, healthy Nordic diet, LC-QQQ-MS, pipecolic acid betaine, quantitative, rye, whole grain
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-402660 (URN)10.1093/ajcn/nqz179 (DOI)000504093300012 ()31504116 (PubMedID)
Funder
NordForsk, 070014Swedish Heart Lung FoundationSwedish Diabetes Association
Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-20Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-8620-4586

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