G(s)alpha deficiency in adipose tissue leads to a lean phenotype with divergent effects on cold tolerance and diet-induced thermogenesis.
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.
Chen
Min
M
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. minc@intra.niddk.nih.gov
Chen
Hui
H
Nguyen
Annie
A
Gupta
Divakar
D
Wang
Jie
J
Lai
Edwin W
EW
Pacak
Karel
K
Gavrilova
Oksana
O
Quon
Michael J
MJ
Weinstein
Lee S
LS
D000064:Acclimatization / Q000502:physiology*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D001774:Blood Chemical Analysis; D003080:Cold Temperature; D004032:Diet; D004734:Energy Metabolism / Q000502:physiology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D010641:Phenotype; D022722:Thermogenesis / Q000502:physiology*
D019205:GTP-Binding Protein alpha Subunits, Gs