title: Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Endocrinology, Rigshospitalet, Section 7652, Tagensvej 20, DK-2200, Copenhagen N, Denmark. linn.gillberg@rh.regionh.dk.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. linn.gillberg@rh.regionh.dk.
authors.forename: Linn
authors.initials: L
authors.lastname: Gillberg
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, SE-20502, Malmö, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Perfilyev
authors.affiliation: Department of Endocrinology, Rigshospitalet, Section 7652, Tagensvej 20, DK-2200, Copenhagen N, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Brøns
authors.affiliation: Department of Endocrinology, Rigshospitalet, Section 7652, Tagensvej 20, DK-2200, Copenhagen N, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Thomasen
authors.affiliation: Department of Endocrinology, Rigshospitalet, Section 7652, Tagensvej 20, DK-2200, Copenhagen N, Denmark.
authors.forename: Louise G
authors.initials: LG
authors.lastname: Grunnet
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, SE-20502, Malmö, Sweden.
authors.forename: Petr
authors.initials: P
authors.lastname: Volkov
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Rosqvist
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.|Center for Clinical Research Dalarna, Falun, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Iggman
authors.affiliation: Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, SE-20502, Malmö, Sweden.
authors.forename: Tina
authors.initials: T
authors.lastname: Rönn
authors.affiliation: Department of Endocrinology, Rigshospitalet, Section 7652, Tagensvej 20, DK-2200, Copenhagen N, Denmark.|Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, SE-20502, Malmö, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Nilsson
authors.affiliation: Department of Endocrinology, Rigshospitalet, Section 7652, Tagensvej 20, DK-2200, Copenhagen N, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, SE-20502, Malmö, Sweden. charlotte.ling@med.lu.se.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D019175:DNA Methylation / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D057890:Epigenomics; D044943:Fatty Acid Desaturases / Q000235:genetics; D006801:Humans; D007230:Infant, Low Birth Weight / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D055815:Young Adult
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; C095992:complexin I; D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human
keywords: Diet; Epigenetics; Gene expression; High-fat overfeeding; Low birthweight; Metabolism; Obesity; Type 2 diabetes