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

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

► Mice with adipose-specific deficiency of the G protein Gsα were generated
► Gsα is required for normal adipogenesis in vivo and in vitro
► Gsα is not imprinted in white adipose tissue
► Mutant mice had opposite effects on cold tolerance and diet-induced thermogenesis