The effects of β3-adrenoceptor agonist CL-316,243 on adiponectin, adiponectin receptors and tumor necrosis factor-α expressions in adipose tissues of obese diabetic KKAy mice

We investigated the effects of β3-adrenoceptor agonist, 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316,243) in obese diabetic KKAy mice. Two weeks' subcutaneous administration of CL-316,243 reduced serum levels of glucose, insulin, triglyceride, free fatty acid and tumor necrosis factor-α (TNF-α), and increased adiponectin. Adiponectin, adiponectin receptors and β3-adrenoceptor mRNA expressions were reduced in epididymal white adipose tissue in KKAy mice, and CL-316,243 recovered these mRNA expressions. Meanwhile, CL-316,243 suppressed the overexpressed mRNA level of TNF-α in both epididymal white adipose tissue and brown adipose tissue. These data suggest that the normalization of adiponectin, adiponectin receptors and TNF-α may result in the amelioration of obesity-induced insulin resistance.