title: Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial.
abstract: 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 ∼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 α (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. This trial was registered at clinicaltrials.gov as NCT01427140.
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Clinical Research Center, Malmö, Sweden.
authors.forename: Alexander
authors.identifier: 0000-0003-1136-8946
authors.initials: A
authors.lastname: Perfilyev
authors.affiliation: Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Ingrid
authors.identifier: 0000-0003-3819-5977
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Diabetes and Metabolism, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark; and.
authors.forename: Linn
authors.identifier: 0000-0003-0588-1663
authors.initials: L
authors.lastname: Gillberg
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.identifier: 0000-0002-8982-6129
authors.initials: F
authors.lastname: Rosqvist
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: David
authors.identifier: 0000-0002-6281-7441
authors.initials: D
authors.lastname: Iggman
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Clinical Research Center, Malmö, Sweden.
authors.forename: Petr
authors.initials: P
authors.lastname: Volkov
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Clinical Research Center, Malmö, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Nilsson
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Ulf
authors.identifier: 0000-0002-8620-4586
authors.initials: U
authors.lastname: Risérus
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Clinical Research Center, Malmö, Sweden; charlotte.ling@med.lu.se.
authors.forename: Charlotte
authors.identifier: 0000-0003-0587-7154
authors.initials: C
authors.lastname: Ling
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004032:Diet; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D002149:Energy Intake; D044127:Epigenesis, Genetic; D005227:Fatty Acids / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005247:Feeding Behavior; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D004247:DNA
keywords: DNA methylation; EWAS; Illumina 450k methylation array; LIPOGAIN cohort; epigenetics; obesity; overfeeding; polyunsaturated fat; prediction; saturated fat