EXPRESSION OF UNCOUPLING PROTEIN IN SKELETAL-MUSCLE AND WHITE FAT OF OBESE MICE TREATED WITH THERMOGENIC BETA-3-ADRENERGIC AGONIST

The mitochondrial uncoupling protein (UCP) is usually expressed only i n brown adipose tissue (BAT) and a key molecule for metabolic thermoge nesis. The effects of a highly selective beta 3-adrenergic agonist, CL 316,243 (CL), on UCP expression in skeletal muscle and adipose tissues were examined in mice. Daily injection of CL (0.1 mg/kg, sc) to obese yellow KK mice for two weeks caused a significant reduction of body w eight, associated with a marked decrease of white fat pad weight and h yper-trophy of the interscapular BAT with a sixfold increase in UCP co ntent, Clear signals of UCP protein and mRNA were detected by Western and Northern blot analyses in inguinal, mesenteric and retroperitoneal white fat pads, and also in gastrocnemius and quadriceps muscles, whe reas no signal in saline-treated mice, The presence of UCP mRNA in mus cle tissues was also confirmed by reverse transcription-PCR analysis, Weaker UCP signals were also detected in control C57BL mice treated wi th CL, but only in inguinal and retroperitoneal fat pads. Immunohistoc hemical examinations revealed that UCP stains in the white fat pads we re localized on multilocular cells quite similar to typical brown adip ocyte, and those in the muscle tissues on myocytes, The mitochondrial localization of UCP in myocytes was confirmed by immunoelectron micros copy. In addition to UCP protein, UCP mRNA was also detected in myocyt es by in situ hybridization analysis, Thus, chronic stimulation of the beta 3-adrenergic receptor induces ectopic expression of UCP in adipo se tissues conventionally considered as white fat and even in skeletal muscle, which probably contributes to the potent anti-obesity effect of the beta 3-adrenergic agonist.