Exercise causes epigenetic changes in fat cells

07 Jul
It seems more and more obvious than rather just burning fat, what exercise does against overweight is to alter the way the body works in more subtle pathways.
Tina Röhn et al., A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue. PLoS Genetics 2013. Open access → LINK [doi:10.1371/journal.pgen.1003572]


Epigenetic mechanisms are implicated in gene regulation and the
development of different diseases. The epigenome differs between cell
types and has until now only been characterized for a few human tissues.
Environmental factors potentially alter the epigenome. Here we describe
the genome-wide pattern of DNA methylation in human adipose tissue from
23 healthy men, with a previous low level of physical activity, before
and after a six months exercise intervention. We also investigate the
differences in adipose tissue DNA methylation between 31 individuals
with or without a family history of type 2 diabetes. DNA methylation was
analyzed using Infinium HumanMethylation450 BeadChip, an array
containing 485,577 probes covering 99% RefSeq genes. Global DNA
methylation changed and 17,975 individual CpG sites in 7,663 unique
genes showed altered levels of DNA methylation after the exercise
intervention (q<0.05). Differential mRNA expression was present in 1/3 of gene regions with altered DNA methylation, including RALBP1, HDAC4 and NCOR2 (q<0.05). Using a luciferase assay, we could show that increased DNA methylation in vitro of the RALBP1 promoter suppressed the transcriptional activity (p
= 0.03). Moreover, 18 obesity and 21 type 2 diabetes candidate genes
had CpG sites with differences in adipose tissue DNA methylation in
response to exercise (q<0.05), including TCF7L2 (6 CpG sites) and KCNQ1
(10 CpG sites). A simultaneous change in mRNA expression was seen for 6
of those genes. To understand if genes that exhibit differential DNA
methylation and mRNA expression in human adipose tissue in vivo affect adipocyte metabolism, we silenced Hdac4 and Ncor2
respectively in 3T3-L1 adipocytes, which resulted in increased
lipogenesis both in the basal and insulin stimulated state. In
conclusion, exercise induces genome-wide changes in DNA methylation in
human adipose tissue, potentially affecting adipocyte metabolism.

Figure 2. Analysis flowchart.
Table 3. Changes in adipose tissue DNA methylation in response to a 6 months exercise intervention. Significant CpG sites (q<0.05) with the biggest change in DNA methylation (>8%).

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Posted by on July 7, 2013 in epigenetics, health, human genetics


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