2. Academic Validation
  3. GSK126 alleviates the obesity phenotype by promoting the differentiation of thermogenic beige adipocytes in diet-induced obese mice

GSK126 alleviates the obesity phenotype by promoting the differentiation of thermogenic beige adipocytes in diet-induced obese mice

  • Biochem Biophys Res Commun. 2018 Jun 18;501(1):9-15. doi: 10.1016/j.bbrc.2018.04.073.
Xiaohui Wu 1,  Yuying Wang 2,  Yingmei Wang 2,  Xinli Wang 3,  Jianqiang Li 4,  Kaixuan Chang 4,  Cheng Sun 4,  Zhen Jia 4,  Song Gao 5,  Jiachang Wei 5,  Jiuhang Xu 5,  Yuqiao Xu 6,  Qing Li 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Cancer Biology, Department of Pathology, The First Affiliated Hospital, Air Force Medical University, Xi'an, 710032, China; China-Nepal Friendship Medical Research Center of Prof. Rajiv Kumar Jha, Xi'an Medical University, Xi'an, 710021, China.
  • 2 State Key Laboratory of Cancer Biology, Department of Pathology, The First Affiliated Hospital, Air Force Medical University, Xi'an, 710032, China.
  • 3 Department of Orthopedics, The First Affiliated Hospital, Air Force Medical University, Xi'an, 710032, China.
  • 4 Cadet Brigade, Air Force Medical University, Xi'an, 710032, China.
  • 5 Aeronautics and Astronautics Clinical Medicine School, Air Force Medical University, Xi'an, 710032, China.
  • 6 State Key Laboratory of Cancer Biology, Department of Pathology, The First Affiliated Hospital, Air Force Medical University, Xi'an, 710032, China. Electronic address: yuqiaoxu@fmmu.edu.cn.
  • 7 State Key Laboratory of Cancer Biology, Department of Pathology, The First Affiliated Hospital, Air Force Medical University, Xi'an, 710032, China. Electronic address: liqing@fmmu.edu.cn.
PMID: 29654753 DOI: 10.1016/j.bbrc.2018.04.073
Abstract

A close relationship between epigenetic regulation and obesity has been demonstrated in several recent studies. Histone Methyltransferase enhancer of Zeste homolog 2 (EZH2), which mainly catalyzes trimethylation of histone H3K27 to form H3K27me3 was found to be required for the differentiation of white and brown adipocytes in vitro. Here, we investigated the effects of the Ezh2-specific inhibitor GSK126 in a mouse model of obesity induced by a high-fat diet (HFD). We found that GSK126 treatment reduced body fat, improved glucose tolerance, increased lipolysis and improved cold tolerance in mice by promoting the differentiation of thermogenic beige adipocytes. Moreover, we discovered that GSK126 inhibited the differentiation of white adipocytes, and the decrease of EZH2 enzymatic activity and H3K27me3 also changed the morphology of brown adipocytes but did not alter the expression of thermogenic genes in these cells. Our results indicated that GSK126 was a novel chemical inducer of beige adipocytes and may be a potential therapeutic agent for the management of obesity. Furthermore, they also prompted that EZH2 and H3K27me3 play different roles in the differentiation of the white, brown, and beige adipocytes in vivo.

Keywords

Beige adipocyte; Ezh2; GSK126; H3K27me3; Obesity.

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