Ablation of LGR4 promotes energy expenditure by driving white-to-brown fat switch.

Jiqiu Wang, Ruixin Liu, Feng Wang, Jie Hong, Xiaoying Li, Maopei Chen, Yingying Ke, Xianfeng Zhang, Qinyun Ma, Rui Wang, Juan Shi, Bin Cui, Weiqiong Gu, Yifei Zhang, Zhiguo Zhang, Weiqing Wang, Xuefeng Xia, Mingyao Liu, Guang Ning

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), specialized for energy expenditure through thermogenesis, potently counteracts obesity. Factors that induce brown adipocyte commitment and energy expenditure would be a promising defence against adiposity. Here, we show that Lgr4 homozygous mutant (Lgr4(m/m)) mice show reduced adiposity and resist dietary and leptin mutant-induced obesity with improved glucose metabolism. Lgr4(m/m) mice show a striking increase in energy expenditure, and exhibit brown-like adipocytes in WAT depots with higher expression of BAT and beige cell markers. Furthermore, Lgr4 ablation potentiates brown adipocyte differentiation from the stromal vascular fraction of epididymal WAT, partially through retinoblastoma 1 gene (Rb1) reduction. A functional low-frequency human LGR4 variant (A750T) has been associated with body mass index in a Chinese obese-versus-control study. Our results identify an important role for LGR4 in energy balance and body weight control through regulating the white-to-brown fat transition.

Original languageEnglish
Pages (from-to)1455-1463
Number of pages9
JournalNature Cell Biology
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2013

ASJC Scopus subject areas

  • Cell Biology

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