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- Title
Loss of Mbd2 Protects Mice Against High-Fat Diet-Induced Obesity and Insulin Resistance by Regulating the Homeostasis of Energy Storage and Expenditure.
- Authors
Cheng, Jia; Song, Jia; He, Xiaoyu; Zhang, Meng; Hu, Shuang; Zhang, Shu; Yu, Qilin; Yang, Ping; Xiong, Fei; Wang, Dao Wen; Zhou, Jianfeng; Ning, Qin; Chen, Zhishui; Eizirik, Decio L; Zhou, Zhiguang; Zhao, Chunxia; Wang, Cong-Yi
- Abstract
Previous studies including ours demonstrated that methyl-CpG-binding domain 2 (MBD2) acts as a reader to decipher DNA methylome-encoded information. We thus in the current study used Mbd2-/- mice as a model to dissect the impact of high-fat diet (HFD) on DNA methylome relevant to the pathoetiology of obesity. It was interestingly noted that mice deficient in Mbd2 were protected from HFD-induced obesity and insulin resistance. Mechanistic study revealed that HFD rendered epididymal adipose tissues to undergo a DNA methylation turnover as evidenced by the changes of methylation levels and patterns. Specifically, HFD was noted with higher potency to induce DNA hypomethylation in genes relevant to energy storage than that in genes associated with energy expenditure. As a result, arrays of genes were subjected to expression changes, which led to an altered homeostasis for energy storage and expenditure in favor of obesity development. Loss of Mbd2 resulted in impaired implementation of above DNA methylation changes associated with altered energy homeostasis, which then protected mice from HFD-induced obesity and insulin resistance. Those data would provide novel insight into the understanding of the pathoetiology underlying obesity with potential for developing effective therapies against obesity in clinical settings.
- Subjects
ANIMAL experimentation; CELL culture; DIET; ENERGY metabolism; GLUCOSE tolerance tests; HOMEOSTASIS; INSULIN; INSULIN resistance; MICE; OBESITY; POLYMERASE chain reaction; WESTERN immunoblotting; DNA-binding proteins; DNA methylation; IN vitro studies
- Publication
Diabetes, 2016, Vol 65, Issue 11, p3384
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-0151