beta 3-adrenergic agonist up-regulates uncoupling proteins 2 and 3 in skeletal muscle of the mouse

Chronic stimulation of the beta3-adrenergic receptor (AR) in obese animals resulted in a reduced adiposity associated with an increased expression of thermogenic uncoupling protein (UCP)1 in adipose tissues. In this study, th e mRNA expression of newly cloned UCP isoforms (UCP2 and UCP3) were examine d in obese yellow KK and C57BL control mice. UCP2 mRNA was found in all tis sues examined, with higher levels in adipose tissues and skeletal muscle of the obese mice. UCP3 mRNA was expressed in skeletal muscle, heart and brow n adipose tissue similarly in the two mouse strains. Daily injection of a s elective beta3-adrenergic agonist, CL316,243 (0.1 mg/kg), for 10 days resul ted in a marked reduction of white fat pad weight and 1.8 similar to4.8-fol d increase in the mRNA levels of UCP2 and UCP3 in skeletal muscle of obese mice. No noticeable change in the UCP2 and 3 mRNA levels was found in brown and white adipose tissues. It was also found that CL316,243 injection prod uced a marked and sustained elevation of the plasma free fatty acid level. These results, together with our previous Endings of the fatty acid-induced UCP expression in a myocyte cell line in vitro, suggest that the beta3-AR agonist-induced UCP expression in skeletal muscle may be mediated through t he elevated plasma free fatty acids. It was also suggested that anti-obesit y effect of beta3-AR agonists is attributable to increased thermogenesis no t only by UCP1 but also by UCP2 and UCP3.