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Rosqvist, Fredrik
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Rosqvist, F., McNeil, C. A., Pramfalk, C., Parry, S. A., Low, W. S., Cornfield, T., . . . Hodson, L. (2019). Fasting hepatic de novo lipogenesis is not reliably assessed using circulating fatty acid markers. American Journal of Clinical Nutrition, 109(2), 260-268
Åpne denne publikasjonen i ny fane eller vindu >>Fasting hepatic de novo lipogenesis is not reliably assessed using circulating fatty acid markers
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2019 (engelsk)Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, nr 2, s. 260-268Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Observational studies often infer hepatic de novo lipogenesis (DNL) by measuring circulating fatty acid (FA) markers; however, it remains to be elucidated whether these markers accurately reflect hepatic DNL. Objectives: We investigated associations between fasting hepatic DNL and proposed FA markers of DNL in subjects consuming their habitual diet. Methods: Fasting hepatic DNL was assessed using (H2O)-H-2(deuterated water) in 149 nondiabetic men and women and measuring the synthesis of very low-density lipoprotein triglyceride (VLDL-TG) palmitate. FA markers of blood lipid fractions were determined by gas chromatography. Results: Neither the lipogenic index (16: 0/18: 2n-6) nor the SCD index (16: 1n-7/16: 0) in VLDL-TG was associated with isotopically assessed DNL (r = 0.13, P = 0.1 and r = -0.08, P = 0.35, respectively). The relative abundances (mol%) of 14: 0, 16: 0, and 18: 0 in VLDL-TG were weakly (r <= 0.35) associated with DNL, whereas the abundances of 16: 1n-7, 18: 1n-7, and 18: 1n-9 were not associated. When the cohort was split by median DNL, only the abundances of 14: 0 and 18: 0 in VLDL-TG could discriminate between subjects having high (11.5%) and low(3.8%) fasting hepatic DNL. Based on a subgroup, FA markers in total plasma TG, plasma cholesteryl esters, plasma phospholipids, and red blood cell phospholipids were generally not associated with DNL. Conclusions: The usefulness of circulating FAs as markers of hepatic DNL in healthy individuals consuming their habitual diet is limited due to their inability to discriminate clearly between individuals with low and high fasting hepatic DNL.

sted, utgiver, år, opplag, sider
Oxford University Press, 2019
Emneord
de novo lipogenesis, fatty acids, metabolism, human, triglycerides, lipogenic index, SCD, palmitoleic acid
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-380498 (URN)10.1093/ajcn/nqy304 (DOI)000460615600005 ()30721918 (PubMedID)
Tilgjengelig fra: 2019-04-23 Laget: 2019-04-23 Sist oppdatert: 2019-04-23bibliografisk kontrollert
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.
Åpne denne publikasjonen i ny fane eller vindu >>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 (engelsk)Inngår i: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 63, nr 13, artikkel-id 1801405Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2019
Emneord
gene-expression, healthy Nordic diet, metabolic syndrome, peripheral blood mononuclear cells, transcriptome
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-390915 (URN)10.1002/mnfr.201801405 (DOI)000473667000001 ()30964598 (PubMedID)
Forskningsfinansiär
Swedish Research CouncilSwedish Heart Lung FoundationNordForsk, 070014Swedish Diabetes Association
Tilgjengelig fra: 2019-08-15 Laget: 2019-08-15 Sist oppdatert: 2019-08-15bibliografisk kontrollert
Straniero, S., Rosqvist, F., Edholm, D., Ahlström, H., Kullberg, J., Sundbom, M., . . . Rudling, M. (2017). Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity. Journal of Internal Medicine, 281(5), 507-517
Åpne denne publikasjonen i ny fane eller vindu >>Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity
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2017 (engelsk)Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, nr 5, s. 507-517Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver.

METHODS: Ten morbidly obese women (BMI 42 ± 2.6 kg m(-2) ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day(-1) ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI <25 kg m(-2) ) served as controls.

RESULTS: At baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%.

CONCLUSIONS: The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.

Emneord
bile acid synthesis, cholesterol synthesis, proprotein convertase subtilisin/kexin type 9
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-316832 (URN)10.1111/joim.12599 (DOI)000399779700009 ()28261926 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2015-02781Swedish Heart Lung Foundation, 20160491Stockholm County Council, ALF 20150447Swedish Diabetes Association
Tilgjengelig fra: 2017-03-07 Laget: 2017-03-07 Sist oppdatert: 2019-08-27bibliografisk kontrollert
Petrus, P., Edholm, D., Rosqvist, F., Dahlman, I., Sundbom, M., Arner, P., . . . Risérus, U. (2017). Depot-specific differences in fatty acid composition and distinct associations with lipogenic gene expression in abdominal adipose tissue of obese women. International Journal of Obesity, 41(8), 1295-1298
Åpne denne publikasjonen i ny fane eller vindu >>Depot-specific differences in fatty acid composition and distinct associations with lipogenic gene expression in abdominal adipose tissue of obese women
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2017 (engelsk)Inngår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, nr 8, s. 1295-1298Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Cardiometabolic diseases are primarily linked to enlarged visceral adipose tissue (VAT). However, some data suggest heterogeneity within the subcutaneous adipose tissue (SAT) depot with potential metabolic differences between the superficial SAT (sSAT) and deep SAT (dSAT) compartments. We aimed to investigate the heterogeneity of these three depots with regard to fatty acid (FA) composition and gene expression. Adipose tissue biopsies were collected from 75 obese women undergoing laparoscopic gastric bypass surgery. FA composition and gene expression were determined with gas chromatography and quantitative real-time-PCR, respectively. Stearoyl CoA desaturase-1 (SCD-1) activity was estimated by product-to-precursor FA ratios. All polyunsaturated FAs (PUFA) with 20 carbons were consistently lower in VAT than either SAT depots, whereas essential PUFA (linoleic acid, 18:2n-6 and α-linolenic acid, 18:3n-3) were similar between all three depots. Lauric and palmitic acid were higher and lower in VAT, respectively. The SCD-1 product palmitoleic acid as well as estimated SCD-1 activity was higher in VAT than SAT. Overall, there was a distinct association pattern between lipid metabolizing genes and individual FAs in VAT. In conclusion, SAT and VAT are two distinct depots with regard to FA composition and expression of key lipogenic genes. However, the small differences between sSAT and dSAT suggest that FA metabolism of SAT is rather homogenous.

HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-333246 (URN)10.1038/ijo.2017.106 (DOI)000407050500023 ()28465608 (PubMedID)
Forskningsfinansiär
Swedish Research Council
Tilgjengelig fra: 2017-11-09 Laget: 2017-11-09 Sist oppdatert: 2017-11-21bibliografisk kontrollert
Rosqvist, F., Bjermo, H., Kullberg, J., Johansson, L., Michaëlsson, K., Ahlström, H., . . . Risérus, U. (2017). Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study. Lipids in Health and Disease, 16, 1-10, Article ID 68.
Åpne denne publikasjonen i ny fane eller vindu >>Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study
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2017 (engelsk)Inngår i: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 16, s. 1-10, artikkel-id 68Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Visceral adipose tissue (VAT) and truncal fat predict cardiometabolic disease. Intervention trials suggest that saturated fatty acids (SFA), e. g. palmitic acid, promote abdominal and liver fat storage whereas polyunsaturated fatty acids (PUFA), e. g. linoleic acid, prevent fat accumulation. Such findings require investigation in population-based studies of older individuals. We aimed to investigate the relationships of serum biomarkers of PUFA intake as well as serum levels of palmitic acid, with abdominal and total adipose tissue content.

Methods: In a population-based sample of 287 elderly subjects in the PIVUS cohort, we assessed fatty acid composition in serum cholesterol esters (CE) and phospholipids (PL) by gas chromatography and the amount of VAT and abdominal subcutaneous (SAT) adipose tissue by magnetic resonance imaging (MRI), liver fat by MR spectroscopy (MRS), and total body fat, trunk fat and leg fat by dual-energy X-ray absorptiometry (DXA). Insulin resistance was estimated by HOMA-IR.

Results: VAT and trunk fat showed the strongest correlation with insulin resistance (r = 0.49, P < 0.001). Linoleic acid in both CE and PL was inversely related to all body fat depots (r = -0.24 to -0.33, P < 0.001) including liver fat measured in a sub-group (r = -0.26, P < 0.05, n = 73), whereas n-3 PUFA showed weak inverse (18: 3n-3) or positive (20: 5n-3) associations. Palmitic acid in CE, but not in PL, was directly correlated with VAT (r = 0.19, P < 0.001) and trunk fat (r = 0.18, P = 0.003). Overall, the significant associations remained after adjusting for energy intake, height, alcohol, sex, smoking, education and physical activity. The inverse correlation between linoleic acid and VAT remained significant after further adjustment for total body fat.

Conclusions: Serum linoleic acid is inversely related to body fat storage including VAT and trunk fat whereas palmitic acid was less consistently but directly associated, in line with recent feeding studies. Considering the close link between VAT and insulin resistance, a potential preventive role of plant-based PUFA in VAT accumulation warrants further study.

Emneord
Adipose tissue distribution, Body fat, Fatty acid, Linoleic acid, Palmitic acid, Polyunsaturated fat, Saturated fat, Visceral adipose tissue
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-319605 (URN)10.1186/s12944-017-0445-2 (DOI)000398222200001 ()28372558 (PubMedID)
Forskningsfinansiär
Swedish Research Council, K2015-54X-22081-04-3EXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes Association
Tilgjengelig fra: 2017-04-06 Laget: 2017-04-06 Sist oppdatert: 2017-11-29bibliografisk kontrollert
Marklund, M., Pingel, R., Rosqvist, F., Lindroos, A. K., Eriksson, J. W., Vessby, B., . . . Risérus, U. (2017). Fatty Acid Proportions in Plasma Cholesterol Esters and Phospholipids Are Positively Correlated in Various Swedish Populations. Journal of Nutrition, 147(11), 2118-2125
Åpne denne publikasjonen i ny fane eller vindu >>Fatty Acid Proportions in Plasma Cholesterol Esters and Phospholipids Are Positively Correlated in Various Swedish Populations
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2017 (engelsk)Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 147, nr 11, s. 2118-2125Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Fatty acid (FA) proportions in cholesterol esters (CEs) and plasma phospholipids are widely used as dietary biomarkers. Information on how proportions in these fractions correlate could have implications for interpretation and use of FA biomarkers in observational and interventional studies. Objective: We investigated correlations between FA proportions in CEs and phospholipids in free-living individuals and assessed how diet-induced alterations of FA proportions correlate between fractions. Methods: Spearman's rank correlation coefficients (rs) between FA proportions (percentage of total FAs) in circulating CEs and phospholipids were calculated separately in 8 individual study populations including Swedish females and males (N = 2052; age range: 11-84 y), and pooled by inverse-variance weighted meta-analysis. In addition, study populations were stratified by age, sex, body mass index (BMI; in kg/m(2)), and diabetes status, and strata-specific rs were pooled by meta-analysis. In 2 randomized trials (N = 79) in which dietary saturated FAs were isocalorically replaced with unsaturated FAs, treatment-wise calculations of rs were conducted between FA changes in CEs and phospholipids. Results: Overall, FA proportions in CEs and phospholipids correlated well and especially strongly for polyunsaturated FAs (PUFAs), with pooled rs (95% CIs) ranging from 0.74 (0.72, 0.76) for a-linolenic acid to 0.92 (0.91, 0.93) for eicosapentaenoic acid. Weak correlations (pooled rs <0.4) were observed only for palmitic acid and stearic acid, with pooled rs (95% CIs): 0.29 (0.24, 0.33) and 0.30 (0.25, 0.34), respectively. Overall, correlations were not affected by age, sex, BMI, or diabetes status. Strong correlations (r(s) >= 0.6) between diet-induced FA changes in CEs and phospholipids were observed for most PUFAs. Conclusions: Proportions of most FAs in CEs and phospholipids ranked individuals similarly, suggesting that FA proportions in these fractions can be used interchangeably in populations of diverse age, sex, body composition, and diabetes status. Caution is advised, however, when comparing results from studies assessing palmitic acid or stearic acid in different lipid fractions.

sted, utgiver, år, opplag, sider
AMER SOC NUTRITION-ASN, 2017
Emneord
fatty acid, biomarker, cholesterol ester, phospholipid, meta-analysis
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-344334 (URN)10.3945/jn.117.254250 (DOI)000417124300014 ()28931585 (PubMedID)
Tilgjengelig fra: 2018-03-07 Laget: 2018-03-07 Sist oppdatert: 2018-03-07bibliografisk kontrollert
Perfilyev, A., Dahlman, I., Gillberg, L., Rosqvist, F., Iggman, D., Volkov, P., . . . Ling, C. (2017). Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial. American Journal of Clinical Nutrition, 105(4), 991-1000
Åpne denne publikasjonen i ny fane eller vindu >>Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial
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2017 (engelsk)Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, nr 4, s. 991-1000Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses. Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial. Design: We studied the effects of 7 wk of excessive SFA (n = 17) or PUFA (n = 14) intake (+750 kcal/d) on the DNA methylation of similar to 450,000 sites in human subcutaneous adipose tissue. Both diets resulted in similar body weight increases. We also combined the data from the 2 groups to examine the overall effect of overfeeding on the DNA methylation in adipose tissue. Results: The DNA methylation of 4875 Cytosine-phosphate-guanine (CpG) sites was affected differently between the 2 diets. Furthermore, both the SFA and PUFA diets increased the mean degree of DNA methylation in adipose tissue, particularly in promoter regions. However, although the mean methylation was changed in 1797 genes [e.g., alpha-ketoglutarate dependent dioxygenase (FTO), interleukin 6 (IL6), insulin receptor (INSR), neuronal growth regulator 1 (NEGR1), and proopiomelanocortin (POMC)] by PUFAs, only 125 genes [e.g., adiponectin, C1Q and collagen domain containing (ADIPOQ)] were changed by SFA overfeeding. In addition, the SFA diet significantly altered the expression of 28 transcripts [e.g., acyl-CoA oxidase 1 (ACOX1) and FAT atypical cadherin 1 (FAT1)], whereas the PUFA diet did not significantly affect gene expression. When the data from the 2 diet groups were combined, the mean methylation of 1444 genes, including fatty acid binding protein 1 (FABP1), fatty acid binding protein 2 (FABP2), melanocortin 2 receptor (MC2R), MC3R, PPARG coactivator 1 alpha (PPARGC1A), and tumor necrosis factor (TNF), was changed in adipose tissue by overfeeding. Moreover, the baseline DNA methylation of 12 CpG sites that was annotated to 9 genes [e.g., mitogen-activated protein kinase 7 (MAPK7), melanin concentrating hormone receptor 1 (MCHR1), and splicing factor SWAP homolog (SFRS8)] was associated with the degree of weight increase in response to extra energy intake. Conclusions: SFA overfeeding and PUFA overfeeding induce distinct epigenetic changes in human adipose tissue. In addition, we present data that suggest that baseline DNA methylation can predict weight increase in response to overfeeding in humans.

sted, utgiver, år, opplag, sider
AMER SOC NUTRITION-ASN, 2017
Emneord
DNA methylation, epigenetics, EWAS, Illumina 450k methylation array, LIPOGAIN cohort, obesity, overfeeding, polyunsaturated fat, prediction, saturated fat
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-322218 (URN)10.3945/ajcn.116.143164 (DOI)000398941700025 ()28275132 (PubMedID)
Forskningsfinansiär
Swedish Research Council, K2015-54X-2208104-3 523-2010-1061Knut and Alice Wallenberg FoundationNovo NordiskSwedish Diabetes Association
Tilgjengelig fra: 2017-05-17 Laget: 2017-05-17 Sist oppdatert: 2017-05-22bibliografisk kontrollert
Marklund, M., Pingel, R., Rosqvist, F., Lindroos, A. K., Eriksson, J., Vessby, B., . . . Risérus, U. (2017). Interrelationships Between Fatty Acid Composition in Plasma Cholesterol Esters and Phospholipids in Men and Women: A Pooled Analysis. Annals of Nutrition and Metabolism, 71, 372-372
Åpne denne publikasjonen i ny fane eller vindu >>Interrelationships Between Fatty Acid Composition in Plasma Cholesterol Esters and Phospholipids in Men and Women: A Pooled Analysis
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2017 (engelsk)Inngår i: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 71, s. 372-372Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
S. Karger, 2017
Emneord
Biomarker, Fatty acid, Cholesterol ester, Phospholipid, Meta-analysis
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-377742 (URN)000415605300664 ()
Tilgjengelig fra: 2019-02-26 Laget: 2019-02-26 Sist oppdatert: 2019-02-26bibliografisk kontrollert
Lankinen, M., Schwab, U., Kolehmainen, M., Paananen, J., Nygren, H., Seppanen-Laakso, T., . . . Oresic, M. (2016). A Healthy Nordic Diet Alters the Plasma Lipidomic Profile in Adults with Features of Metabolic Syndrome in a Multicenter Randomized Dietary Intervention. Journal of Nutrition, 146(4), 662-672
Åpne denne publikasjonen i ny fane eller vindu >>A Healthy Nordic Diet Alters the Plasma Lipidomic Profile in Adults with Features of Metabolic Syndrome in a Multicenter Randomized Dietary Intervention
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2016 (engelsk)Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 146, nr 4, s. 662-672Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: A healthy Nordic diet is associated with improvements in cardiometabolic risk factors, but the effect on lipidomic profile is not known.

Objective: The aim was to investigate how a healthy Nordic diet affects the fasting plasma lipidomic profile in subjects with metabolic syndrome.

Methods: Men and women (n = 200) with features of metabolic syndrome [mean age: 55 y; body mass index (in kg/m(2)): 31.6] were randomly assigned to either a healthy Nordic (n = 104) or a control (n = 96) diet for 18 or 24 wk at 6 centers. Of the participants, 156 completed the study with plasma lipidomic measurements. The healthy Nordic diet consisted of whole grains, fruits, vegetables, berries, vegetable oils and margarines, fish, low-fat milk products, and low-fat meat. An average Nordic diet served as the control diet and included low-fiber cereal products, dairy fat-based spreads, regular-fatmilk products, and a limited amount of fruits, vegetables, and berries. Lipidomic profiles were measured at baseline, week 12, and the end of the intervention (18 or 24wk) by using ultraperformance liquid chromatography mass spectrometry. The effects of the diets on the lipid variables were analyzed with linear mixed-effects models. Data from centers with 18- or 24-wk duration were also analyzed separately.

Results: Changes in 21 plasma lipids differed significantly between the groups at week 12 (false discovery rate P < 0.05), including increases in plasmalogens and decreases in ceramides in the healthy Nordic diet group compared with the control group. At the end of the study, changes in lipidomic profiles did not differ between the groups. However, when the intervention lasted 24 wk, changes in 8 plasma lipids that had been identified at 12 wk, including plasmalogens, were sustained. There were no differences in changes in plasma lipids between groups with an intervention of 18 wk. By the dietary biomarker score, adherence to diet did not explain the difference in the results related to the duration of the study.

Conclusions: A healthy Nordic diet transiently modified the plasma lipidomic profile, specifically by increasing the concentrations of antioxidative plasmalogens and decreasing insulin resistance-inducing ceramides.

Emneord
Nordic diet, randomized controlled trial, nutrition, lipidomics, lipids, human
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-295554 (URN)10.3945/jn.115.220459 (DOI)000373415000002 ()
Forskningsfinansiär
Swedish Heart Lung FoundationSwedish Diabetes Association
Tilgjengelig fra: 2016-06-08 Laget: 2016-06-08 Sist oppdatert: 2017-11-30bibliografisk kontrollert
Gillberg, L., Perfilyev, A., Brons, C., Thomasen, M., Grunnet, L. G., Volkov, P., . . . Ling, C. (2016). Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding. Diabetologia, 59(4), 799-812
Åpne denne publikasjonen i ny fane eller vindu >>Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding
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2016 (engelsk)Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, nr 4, s. 799-812Artikkel i tidsskrift (Fagfellevurdert) Published
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.

Emneord
Diet, Epigenetics, Gene expression, High-fat overfeeding, Low birthweight, Metabolism, Obesity, Type 2 diabetes
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-282787 (URN)10.1007/s00125-015-3852-9 (DOI)000371802700018 ()26750116 (PubMedID)
Forskningsfinansiär
Swedish Research CouncilRegion SkåneKnut and Alice Wallenberg FoundationEXODIAB - Excellence of Diabetes Research in Sweden, B31 5631/2006Swedish Diabetes Association
Tilgjengelig fra: 2016-04-13 Laget: 2016-04-07 Sist oppdatert: 2017-11-30bibliografisk kontrollert
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