The Cannabinoid CB1 Receptor Antagonist SR141716 Increases Acrp30 mRNA Expression in Adipose Tissue of Obese fa/fa Rats and in Cultured Adipocyte Cells

• DOI: 10.1124/mol.63.4.908
• Publication Date: 2003-03-18T18:52:52Z
• Authors: M. Bensaid; M. Gary-Bobo; A. Esclangon; J.P. Maffrand; G. Le Fur; F. Oury-Donat; P. Soubrié
• Keywords: Adipose tissue macrophages; Hyperinsulinemia

This study investigates the effects of SR141716, a selective CB₁ receptor antagonist that reduces food intake and body weight rodents, on Acrp30 mRNA expression in adipose tissue. Acrp30, plasma protein exclusively expressed secreted by tissue, has been shown to induce free fatty acid oxidation, hyperglycemia hyperinsulinemia decrease, reduction. We report that<i>N</i>-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1<i>H</i>-pyrazole-3-carboximide hydrochloride (SR141716) treatment once daily (10 mg/kg/d, i.p.) from 2 14 days reduced stimulated tissue obese Zucker (fa/fa) rats. In parallel, associated with this animal model was SR141716 treatment. cultured mouse adipocytes (3T3 F442A), (25 100 nM) also induced an overexpression protein. addition, CB₁-receptor knockout mice, had no effect expression, demonstrating mediating effect. Furthermore, RT-PCR analysis revealed rat 3T3 F442A mRNA. Relative quantification up-regulation (3- 4-fold) rats differentiated compared lean undifferentiated adipocytes, respectively. Western blot presence CB₁receptors their up-regulated cells. These results show hormonal regulations may participate reduction suggest role metabolic regulation antiobesity SR141716.