Young men with low birthweight exhibit decreased plasticity of genome-wide muscle DNA methylation by high-fat overfeeding

TY - JOUR

T1 - Young men with low birthweight exhibit decreased plasticity of genome-wide muscle DNA methylation by high-fat overfeeding

AU - Jacobsen, Stine C

AU - Gillberg, Linn

AU - Bork-Jensen, Jette

AU - Ribel-Madsen, Rasmus

AU - Lara, Ester

AU - Calvanese, Vincenzo

AU - Ling, Charlotte

AU - Fernandez, Agustin F

AU - Fraga, Mario F

AU - Poulsen, Pernille

AU - Brøns, Charlotte

AU - Vaag, Allan

PY - 2014/6

Y1 - 2014/6

N2 - Aims/hypothesis: The association between low birthweight (LBW) and risk of developing type 2 diabetes may involve epigenetic mechanisms, with skeletal muscle being a prime target tissue. Differential DNA methylation patterns have been observed in single genes in muscle tissue from type 2 diabetic and LBW individuals, and we recently showed multiple DNA methylation changes during short-term high-fat overfeeding in muscle of healthy people. In a randomised crossover study, we analysed genome-wide DNA promoter methylation in skeletal muscle of 17 young LBW men and 23 matched normal birthweight (NBW) men after a control and a 5 day high-fat overfeeding diet. Methods: DNA methylation was measured using Illumina's Infinium BeadArray covering 27,578 CpG sites representing 14,475 different genes. Results: After correction for multiple comparisons, DNA methylation levels were found to be similar in the LBW and NBW groups during the control diet. Whereas widespread DNA methylation changes were observed in the NBW group in response to high-fat overfeeding, only a few methylation changes were seen in the LBW group (χ2, p∈<∈0.001). Conclusions/interpretation: Our results indicate lower DNA methylation plasticity in skeletal muscle from LBW vs NBW men, potentially contributing to understanding the link between LBW and increased risk of type 2 diabetes.

AB - Aims/hypothesis: The association between low birthweight (LBW) and risk of developing type 2 diabetes may involve epigenetic mechanisms, with skeletal muscle being a prime target tissue. Differential DNA methylation patterns have been observed in single genes in muscle tissue from type 2 diabetic and LBW individuals, and we recently showed multiple DNA methylation changes during short-term high-fat overfeeding in muscle of healthy people. In a randomised crossover study, we analysed genome-wide DNA promoter methylation in skeletal muscle of 17 young LBW men and 23 matched normal birthweight (NBW) men after a control and a 5 day high-fat overfeeding diet. Methods: DNA methylation was measured using Illumina's Infinium BeadArray covering 27,578 CpG sites representing 14,475 different genes. Results: After correction for multiple comparisons, DNA methylation levels were found to be similar in the LBW and NBW groups during the control diet. Whereas widespread DNA methylation changes were observed in the NBW group in response to high-fat overfeeding, only a few methylation changes were seen in the LBW group (χ2, p∈<∈0.001). Conclusions/interpretation: Our results indicate lower DNA methylation plasticity in skeletal muscle from LBW vs NBW men, potentially contributing to understanding the link between LBW and increased risk of type 2 diabetes.

U2 - 10.1007/s00125-014-3198-8

DO - 10.1007/s00125-014-3198-8

M3 - Journal article

C2 - 24570141

SN - 0012-186X

VL - 57

SP - 1154

EP - 1158

JO - Diabetologia

JF - Diabetologia

IS - 6

ER -