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Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial
Lund Univ, Clin Res Ctr, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmo, Sweden..
Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
Rigshosp, Dept Endocrinol, Diabet & Metab, Copenhagen, Denmark..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
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2017 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, no 4, 991-1000 p.Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
AMER SOC NUTRITION-ASN , 2017. Vol. 105, no 4, 991-1000 p.
Keyword [en]
DNA methylation, epigenetics, EWAS, Illumina 450k methylation array, LIPOGAIN cohort, obesity, overfeeding, polyunsaturated fat, prediction, saturated fat
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:uu:diva-322218DOI: 10.3945/ajcn.116.143164ISI: 000398941700025PubMedID: 28275132OAI: oai:DiVA.org:uu-322218DiVA: diva2:1096388
Funder
Swedish Research Council, K2015-54X-2208104-3 523-2010-1061Knut and Alice Wallenberg FoundationNovo NordiskSwedish Diabetes Association
Available from: 2017-05-17 Created: 2017-05-17 Last updated: 2017-05-22Bibliographically approved

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