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Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance
| Content Provider | Paperity |
|---|---|
| Author | Xu, Aimin Shin, Kyung Cheul Kwak, Soo-heon Alfadda, Assim A. Kim, A. Young Park, Yoon Jeong Pan, Xuebo Sallam, Reem M. Bassas, Abdulelah F. Kim, Jae Bum Park, Kyong Soo |
| Abstract | Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases. |
| File Format | HTM / HTML |
| DOI | 10.1038/ncomms8585 |
| Journal | Nature Communications |
| Volume Number | 6 |
| e-ISSN | 20411723 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2015-07-03 |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
