TY - JOUR
T1 - Adipose tissue transcriptomics and epigenomics in low birthweight men and controls
T2 - role of high-fat overfeeding
AU - Gillberg, Linn
AU - Perfilyev, Alexander
AU - Brøns, Charlotte
AU - Thomasen, Martin
AU - Grunnet, Louise G.
AU - Volkov, Petr
AU - Rosqvist, Fredrik
AU - Iggman, David
AU - Dahlman, Ingrid
AU - Risérus, Ulf
AU - Rönn, Tina
AU - Nilsson, Emma
AU - Vaag, Allan
AU - Ling, Charlotte
PY - 2016/4
Y1 - 2016/4
N2 - 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.
AB - 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.
KW - Diet
KW - Epigenetics
KW - Gene expression
KW - High-fat overfeeding
KW - Low birthweight
KW - Metabolism
KW - Obesity
KW - Type 2 diabetes
U2 - 10.1007/s00125-015-3852-9
DO - 10.1007/s00125-015-3852-9
M3 - Journal article
C2 - 26750116
AN - SCOPUS:84959547501
SN - 0012-186X
VL - 59
SP - 799
EP - 812
JO - Diabetologia
JF - Diabetologia
IS - 4
ER -
