Ablation of LGR4 promotes energy expenditure by driving white-to-brown fat switch
Ablation of LGR4 promotes energy expenditure by driving white-to-brown fat switch
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LGR4 的消融通过驱动白色脂肪转变为棕色脂肪来促进能量消耗
DOI：
10.1038/ncb2867
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发表时间：
2013-12-01
影响因子：
21.3
通讯作者：
Ning, Guang
中科院分区：
文献类型：
--
作者：
Wang, Jiqiu;Liu, Ruixin;Ning, Guang
当多余的能量积聚在白色脂肪组织（WAT）中时，肥胖就会发生，而棕色脂肪组织（BAT）通过产热专门用于能量消耗，有效地抵消肥胖。诱导棕色脂肪细胞定型和能量消耗的因素将是一种有希望的防御肥胖。在这里，我们表明，Lgr 4纯合子突变（Lgr 4（m/m））小鼠显示减少肥胖和抵抗饮食和瘦素突变诱导的肥胖与改善葡萄糖代谢。Lgr 4（m/m）小鼠显示出能量消耗的显著增加，并且在WAT贮库中表现出棕色样脂肪细胞，具有较高的BAT和米色细胞标志物表达。此外，Lgr 4去除部分通过视网膜母细胞瘤1基因（Rb 1）减少，增强了附睾WAT基质血管部分的棕色脂肪细胞分化。在一项中国肥胖对照研究中，一种功能性低频人类LGR 4变体（A750 T）与体重指数相关。我们的研究结果确定了LGR 4在能量平衡和体重控制中的重要作用，通过调节白色到棕色脂肪的转变。
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.