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Article: Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance

TitleObesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance
Authors
Issue Date2015
Citation
Nature Communications, 2015, v. 6, article no. 7585 How to Cite?
AbstractAdiponectin 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.
Persistent Identifierhttp://hdl.handle.net/10722/214330

 

DC FieldValueLanguage
dc.contributor.authorKim, AY-
dc.contributor.authorPark, YJ-
dc.contributor.authorPan, X-
dc.contributor.authorShin, KC-
dc.contributor.authorKwak, SH-
dc.contributor.authorBassas, AF-
dc.contributor.authorSallam, RM-
dc.contributor.authorPark, KS-
dc.contributor.authorAlfadda, AA-
dc.contributor.authorXu, A-
dc.date.accessioned2015-08-21T11:15:32Z-
dc.date.available2015-08-21T11:15:32Z-
dc.date.issued2015-
dc.identifier.citationNature Communications, 2015, v. 6, article no. 7585-
dc.identifier.urihttp://hdl.handle.net/10722/214330-
dc.description.abstractAdiponectin 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.-
dc.languageeng-
dc.relation.ispartofNature Communications-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleObesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance-
dc.typeArticle-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/ncomms8585-
dc.identifier.hkuros246886-
dc.identifier.volume6-
dc.identifier.spagearticle no. 7585-
dc.identifier.epagearticle no. 7585-

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