ANTIOBESITY EFFECT OF CL-316,243, A HIGHLY SPECIFIC BETA(3)-ADRENOCEPTOR AGONIST, IN MICE WITH MONOSODIUM-L-GLUTAMATE-INDUCED OBESITY

The effects of CL 316,243, a highly specific beta(3)-adrenoceptor agonist (relative selectivities of 0, 1 and 100 000 for beta(1)-, beta(2)- and beta(3)-receptors, respectively), were evaluated in mice with monosodium L-glutamate (MSG)-induced obesity as well as in control mice injected with physiological saline instead of MSG. Both MSG- and saline-treated mice were divided into three groups and at 8 weeks of age received either CL 316,243 (0.1 or 1.0 mg/kg) or distilled water through a gastric tube for 2 weeks. CL 316,243 not only reduced white adipose tissue mass but also activated brown adipose tissue and systemic metabolism, and hence reduced body mass without affecting food intake. Furthermore, CL 316,243 decreased hyperglycemia and hypertriglyceridemia in MSG-treated mice. However, at the higher dose, CL 316,243 also increased liver triglyceride in MSG-treated mice. These observations suggest that CL 316,243 exerts an anti-obesity effect in mice with MSG-induced obesity and consequently may prove efficacious in the treatment of human obesity.