Lkb1 controls brown adipose tissue growth and thermogenesis by regulating the intracellular localization of CRTC3

Tizhong Shan, Yan Xiong, Pengpeng Zhang, Zhiguo Li, Qingyang Jiang, Pengpeng Bi, Feng Yue, Gongshe Yang, Yizhen Wang, Xiaoqi Liu and Shihuan Kuang ()
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Tizhong Shan: Purdue University
Yan Xiong: Purdue University
Pengpeng Zhang: Purdue University
Zhiguo Li: Purdue University
Qingyang Jiang: Purdue University
Pengpeng Bi: Purdue University
Feng Yue: Purdue University
Gongshe Yang: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University
Yizhen Wang: College of Animal Sciences, Zhejiang University
Xiaoqi Liu: Purdue University
Shihuan Kuang: Purdue University

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Brown adipose tissue (BAT) dissipates energy through Ucp1-mediated uncoupled respiration and its activation may represent a therapeutic strategy to combat obesity. Here we show that Lkb1 controls BAT expansion and UCP1 expression in mice. We generate adipocyte-specific Lkb1 knockout mice and show that, compared with wild-type littermates, these mice exhibit elevated UCP1 expression in BAT and subcutaneous white adipose tissue, have increased BAT mass and higher energy expenditure. Consequently, KO mice have improved glucose tolerance and insulin sensitivity, and are more resistant to high-fat diet (HFD)-induced obesity. Deletion of Lkb1 results in a cytoplasm to nuclear translocation of CRTC3 in brown adipocytes, where it recruits C/EBPβ to enhance Ucp1 transcription. In parallel, the absence of Lkb1 also suppresses AMPK activity, leading to activation of the mTOR signalling pathway and subsequent BAT expansion. These data suggest that inhibition of Lkb1 or its downstream signalling in adipocytes could be a novel strategy to increase energy expenditure in the context of obesity, diabetes and other metabolic diseases.

Date: 2016
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DOI: 10.1038/ncomms12205

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