Glyburide Regulates UCP1 Expression in Adipocytes Independent of KATP Channel Blockade

  • iScience. 2020 Aug 10;23(9):101446. doi: 10.1016/j.isci.2020.101446.
Yan Qiu  1 ,  Yuanyuan Yang  1 ,  Yuda Wei  1 ,  Xiaojian Liu  1 ,  Zhuanghui Feng  1 ,  Xuwen Zeng  2 ,  Yanhao Chen  1 ,  Yan Liu  1 ,  Yongxu Zhao  1 ,  Lanlan Chen  1 ,  Lijun Luo  2 ,  Qiurong Ding  3
Affiliations
  • 1. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, P. R. China.
  • 2. The Affiliated Stomatology Hospital of Tongji University, 399 Yanchang Road, Shanghai 200072, P. R. China.
  • 3. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, P. R. China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, P. R. China. Electronic address: [email protected].
PMID: 32829287 DOI: 10.1016/j.isci.2020.101446
Abstract

Identification of safe and effective compounds to increase or activate UCP1 expression in brown or white adipocytes remains a potent therapeutic strategy to combat obesity. Here we reported that, glyburide, one of the FDA-approved drugs currently used to treat type 2 diabetes, can significantly enhance UCP1 expression in both brown and white adipocytes. Glyburide-fed mice exhibited a clear resistance to high-fat diet-induced obesity, reduced blood triglyceride level, and increased UCP1 expression in brown adipose tissue. Moreover, in situ injection of glyburide to inguinal white adipose tissue remarkably enhanced UCP1 expression and increased thermogenesis. Further mechanistic studies indicated that the glyburide effect in UCP1 expression in adipocytes was KATP channel independent but may involve the regulation of the CA2+-Calcineurin-NFAT signal pathway. Overall, our findings revealed the significant effects of glyburide in regulating UCP1 expression and thermogenesis in adipocytes, which can be potentially repurposed to treat obesity.

Keywords
Human Metabolism; Molecular Biology.
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