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

被引：33

作者：

Chen, Min ^{[1
]}

Chen, Hui ^{[2
]}

Nguyen, Annie ^{[1
]}

Gupta, Divakar ^{[1
]}

Wang, Jie ^{[1
]}

Lai, Edwin W. ^{[3
]}

Pacak, Karel ^{[3
]}

Gavrilova, Oksana ^{[4
]}

Quon, Michael J. ^{[2
]}

Weinstein, Lee S. ^{[1
]}

机构：

[1] NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA

[2] Natl Ctr Complementary & Alternat Med, Clin Invest Lab, Diabet Unit, Bethesda, MD 20892 USA

[3] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, Bethesda, MD 20892 USA

[4] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA

来源：

CELL METABOLISM | 2010年 / 11卷 / 04期

关键词：

HIGH-FAT DIETS; GS-ALPHA GENE; INSULIN-RESISTANCE; INDUCED OBESITY; UCP1-INDEPENDENT THERMOGENESIS; MUSCLE MITOCHONDRIA; ENERGY-EXPENDITURE; MICE LACKING; GNAS GENE; PROTEIN;

D O I：

10.1016/j.cmet.2010.02.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

G(s)alpha, the G protein that mediates receptor-stimulated cAMP generation, has been implicated as a regulator of adipogenesis and adipose tissue function. Heterozygous G(s)alpha mutations lead to obesity in Albright hereditary osteodystrophy (AHO) patients and in mice. In this study, we generated mice with adipose-specific G(s)alpha deficiency. Heterozygotes had 50% loss of G(s)alpha expression in adipose tissue and no obvious phenotype, suggesting that adipose-specific G(s)alpha deficiency is not the cause of obesity in AHO. Homozygotes (FGsKO) had severely reduced adipose tissue, indicating that G(s)alpha 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.

引用

页码：320 / 330

页数：11

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[1] Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver [J].