G_sα Deficiency in Adipose Tissue Leads to a Lean Phenotype with Divergent Effects on Cold Tolerance and Diet-Induced Thermogenesis

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• 作者：Min Chen ; Hui Chen ; Annie Nguyen ; Divakar Gupta ; Jie Wang ; Edwin W. Lai ; Karel Pacak ; Oksana Gavrilova ; Michael J. Quon ; Lee S. Weinstein
• 刊名：Cell Metabolism
• 出版年：2010
• 出版时间：7 April 2010
• 年：2010
• 卷：11
• 期：4
• 页码：320-330
• 全文大小：1299 K

文摘

Summary

G_sα, the G protein that mediates receptor-stimulated cAMP generation, has been implicated as a regulator of adipogenesis and adipose tissue function. Heterozygous G_sα mutations lead to obesity in Albright hereditary osteodystrophy (AHO) patients and in mice. In this study, we generated mice with adipose-specific G_sα deficiency. Heterozygotes had 50 % loss of G_sα expression in adipose tissue and no obvious phenotype, suggesting that adipose-specific G_sα deficiency is not the cause of obesity in AHO. Homozygotes (FGsKO) had severely reduced adipose tissue, indicating that G_sα is required for adipogenesis. Although FGsKO mice had impaired cold tolerance and reduced responsiveness of brown adipose tissue (BAT) to sympathetic signaling, diet-induced thermogenesis and fatty acid oxidation in skeletal muscle were increased. In normal mice, high-fat diet raised sympathetic nerve activity in muscle, but not in BAT. Our results show that cold- and diet-induced thermogenesis may occur in separate tissues, especially when BAT function is impaired.