Abstract
DNA methylation provides a mechanism by which environmental factors can control insulin sensitivity in obesity. Here, we assessed DNA methylation in skeletal muscle from obese people before and after Roux-en-Y gastric bypass (RYGB). Obesity was associated with altered expression of a subset of genes enriched in metabolic process and mitochondrial function. After weight loss, the expression of the majority of the identified genes was normalized to levels observed in normal-weight, healthy controls. Among the 14 metabolic genes analyzed, promoter methylation of 11 genes was normalized to levels observed in the normal-weight, healthy subjects. Using bisulfite sequencing, we show that promoter methylation of PGC-1α and PDK4 is altered with obesity and restored to nonobese levels after RYGB-induced weight loss. A genome-wide DNA methylation analysis of skeletal muscle revealed that obesity is associated with hypermethylation at CpG shores and exonic regions close to transcription start sites. Our results provide evidence that obesity and RYGB-induced weight loss have a dynamic effect on the epigenome.
| Original language | English |
|---|---|
| Journal | Cell Reports |
| Volume | 3 |
| Issue number | 4 |
| Pages (from-to) | 1020-1027 |
| Number of pages | 8 |
| DOIs | |
| Publication status | Published - 25.04.2013 |
Funding
The Strategic Diabetes Program at Karolinska Institutet, The European Foundation for the Study of Diabetes, European Research Council Ideas Program (ICEBERG, ERC-2008-AdG23285), European Molecular Biology Organization (EMBO), Swedish Research Council, Swedish Diabetes Association, Strategic Research Foundation, Knut and Alice Wallenberg Foundation, Stockholm County Council, and Novo Nordisk Research Foundation supported this research. We thank Dr. C. Workman, Dr. F. De Masi, and Dr. S. Rasmussen, Technical University of Denmark, for advice on genome-wide methylation analysis.
