Journal
CELLULAR SIGNALLING
Volume 23, Issue 8, Pages 1375-1386Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2011.03.020
Keywords
RGS protein; RGS2; G protein; Adipocyte differentiation; Lean mouse model
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Funding
- Canadian Institutes for Health Research (CIHR)
- Heart and Stroke Foundation of Ontario (HSFO)
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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 (21-24 month) 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 (4-8 months) 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 gamma (PPAR gamma); lipoprotein lipase (Lpl); CCAAT/enhancer binding protein alpha (CEBP alpha)) 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 degrees 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. (C) 2011 Elsevier Inc. All rights reserved.
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