Resistance to age-related, normal body weight gain in RGS2 deficient mice

Caroline Nunn, Peishen Zhao, Min Xu Zou, Kelly M Summers, Christopher G. Guglielmo, Peter Chidiac

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14 Citations (Scopus)

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 (7h 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.

Original languageEnglish
Pages (from-to)1375-1386
Number of pages12
JournalCellular Signalling
Volume23
Issue number8
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Keywords

  • Adipocyte differentiation
  • G protein
  • Lean mouse model
  • RGS protein
  • RGS2

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