title: Resistance to age-related, normal body weight gain in RGS2 deficient mice.
abstract: RGS2 (regulator of G protein signaling 2) is known to limit signals mediated via Gq- and Gs-coupled GPCRs (G protein coupled receptors), and it has been implicated in the differentiation of several cells types. The physiology of RGS2 knockout mice (rgs2(-/-)) has been studied in some detail, however, a metabolic phenotype has not previously been reported. We observed that old (21-24month) rgs2(-/-) mice weigh much less than wild-type C57BL/6 controls, and exhibit greatly reduced fat deposits, decreased serum lipids, and low leptin levels. Lower weight was evident as early as four weeks and continued throughout life. Younger adult male rgs2(-/-) mice (4-8months) were found to show similar strain-related differences as the aged animals, as well improved glucose clearance and insulin sensitivity, and enhanced beta-adrenergic and glucagon signaling in isolated hepatocytes. In addition, rgs2(-/-) pre-adipocytes had reduced levels of differentiation markers (Peroxisome proliferator-activated receptor γ (PPARγ); lipoprotein lipase (Lpl); CCAAT/enhancer binding protein α (CEBPα)) and also rgs2(-/-) white adipocytes were small relative to controls, suggesting altered adipogenesis. In wild-type animals, RGS2 mRNA was decreased in brown adipose tissue after cold exposure (7 h at 4 °C) but increased in white adipose tissue in response to a high fat diet, also suggesting a role in lipid storage. No differences between strains were detected with respect to food intake, energy expenditure, GPCR-stimulated lipolysis, or adaptive thermogenesis. In conclusion this study points to RGS2 as being an important regulatory factor in controlling body weight and adipose function.
authors: Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.
authors: Caroline
authors: C
authors: Nunn
authors: Peishen
authors: P
authors: Zhao
authors: Min-Xu
authors: MX
authors: Zou
authors: Kelly
authors: K
authors: Summers
authors: Christopher G
authors: CG
authors: Guglielmo
authors: Peter
authors: P
authors: Chidiac
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism; D052438:Adipocytes, White / Q000378:metabolism; D000375:Aging; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D003080:Cold Temperature; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction; D015430:Weight Gain
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D007328:Insulin; D047495:PPAR gamma; D020710:RGS Proteins; D011943:Receptors, Adrenergic, beta; C105345:Rgs2 protein, mouse; D008071:Lipoprotein Lipase; D005947:Glucose