title: Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight.
abstract: Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsα signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight.
authors.affiliation: Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Yong-Qi
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Yogendra B
authors.initials: YB
authors.lastname: Shrestha
authors.affiliation: Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Mouse Metabolism Core Laboratory, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Chanturiya
authors.affiliation: Mouse Metabolism Core Laboratory, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Oksana
authors.initials: O
authors.lastname: Gavrilova
authors.affiliation: Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; leew@mail.nih.gov.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Weinstein
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000172:deficiency* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D050155:Lipogenesis / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects; D018345:Mice, Knockout; D009043:Motor Activity; D009132:Muscles / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D022722:Thermogenesis / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D007328:Insulin; D014280:Triglycerides; D000263:Adenylate Kinase; D019205:GTP-Binding Protein alpha Subunits, Gs; D005947:Glucose
keywords: G proteins; adipocyte; brown adipose tissue; insulin sensitivity; lipid metabolism