KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch signaling

in Journal of Endocrinology
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  • 1 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
  • | 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
  • | 3 Department of Gerontology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China

Correspondence should be addressed to P Cheng or Y Huang: cphh@sohu.com or yanhuang1018@csu.edu.cn
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Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high-fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression-suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of Notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.

 

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