Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding

Linn Gillberg; Alexander Perfilyev; Charlotte Brøns; Martin  Thomasen; Louise G. Grunnet; Petr Volkov; Fredrik Rosqvist; David Iggman; Ingrid Dahlman; Ulf Risérus; Tina Rönn; Emma Nilsson; Allan Vaag; Charlotte Ling

doi:10.1007/s00125-015-3852-9

Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding

Linn Gillberg^*, Alexander Perfilyev, Charlotte Brøns, Martin Thomasen, Louise G. Grunnet, Petr Volkov, Fredrik Rosqvist, David Iggman, Ingrid Dahlman, Ulf Risérus, Tina Rönn, Emma Nilsson, Allan Vaag, Charlotte Ling

^*Corresponding author for this work

Department of Clinical Medicine

40 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Diabetologia
Volume	59
Issue number	4
Pages (from-to)	799-812
Number of pages	14
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-015-3852-9
Publication status	Published - Apr 2016

Keywords

Diet
Epigenetics
Gene expression
High-fat overfeeding
Low birthweight
Metabolism
Obesity
Type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Gillberg, L., Perfilyev, A., Brøns, C., Thomasen, M., Grunnet, L. G., Volkov, P., Rosqvist, F., Iggman, D., Dahlman, I., Risérus, U., Rönn, T., Nilsson, E., Vaag, A., & Ling, C. (2016). Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding. Diabetologia, 59(4), 799-812. https://doi.org/10.1007/s00125-015-3852-9

Gillberg, L, Perfilyev, A, Brøns, C, Thomasen, M, Grunnet, LG, Volkov, P, Rosqvist, F, Iggman, D, Dahlman, I, Risérus, U, Rönn, T, Nilsson, E, Vaag, A & Ling, C 2016, 'Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding', Diabetologia, vol. 59, no. 4, pp. 799-812. https://doi.org/10.1007/s00125-015-3852-9

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abstract = "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.",

keywords = "Diet, Epigenetics, Gene expression, High-fat overfeeding, Low birthweight, Metabolism, Obesity, Type 2 diabetes",

author = "Linn Gillberg and Alexander Perfilyev and Charlotte Br{\o}ns and Martin Thomasen and Grunnet, {Louise G.} and Petr Volkov and Fredrik Rosqvist and David Iggman and Ingrid Dahlman and Ulf Ris{\'e}rus and Tina R{\"o}nn and Emma Nilsson and Allan Vaag and Charlotte Ling",

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doi = "10.1007/s00125-015-3852-9",

language = "English",

volume = "59",

pages = "799--812",

journal = "Diabetologia",

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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 -

Adipose tissue transcriptomics and epigenomics in low birthweight men and controls: role of high-fat overfeeding

Abstract

Keywords

UN SDGs

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