KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch signaling. Issue 3 (13th January 2022)

• Record Type: Journal Article
• Authors: Ye, Ming-sheng; Luo, Liping; Guo, Qi; Su, Tian; Cheng, Peng; Huang, Yan
• Is Part Of: Journal of endocrinology. Volume 252:Issue 3(2022)
• Page Start: 155
• Page End: 166
• Publication Date: 2022-01-13
• Subjects: adipose tissue -- KCTD10 -- thermogenesis -- Notch -- BAT; Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/JOE-21-0016
• Languages: English
• ISSNs: 0022-0795

Abstract

Abstract : 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.