Up-regulation of muscle UCP2 gene expression by a new β3-adrenoceptor agonist, trecadrine, in obese (cafeteria) rodents, but down-regulation in lean animals

OBJECTIVE: The anti-obesity properties of a new beta(3)-adrenergic agonist (Trecadrine) were examined in a diet-induced obesity model, including the effects on OB and uncoupling protein (UCP-1 and -2) gene expression. MEASUREMENTS: Control rats and cafeteria-fed rats were treated with placebo or Trecadrine for 35 days. Leptin and UCP (1 and 2) mRNA levels were determined by reverse transcription-polymerase chain reaction (RT-PCR) methodology in adipose tissue and gastrocnemius muscle. RESULTS: Animals fed a cafeteria diet increased body weight, fat content, white adipose tissue (WAT), brown adipose tissue (BAT) weights and oxygen consumption in relation to lean controls. A rise in plasma leptin, WAT OB gene expression as well as circulating free fatty acids levels was found in obese rats as compared with lean controls. Trecadrine administration to cafeteria-fed animals decreased fat content, WAT weight, circulating leptin and fatty acids concentrations, and WAT OB gene expression, reaching comparable values to lean controls, while WAT O-2 consumption was increased in these animals. Also, an increase in BAT UCP1 mRNA levels was found through a two-way analysis of variance in control and obese animals after Trecadrine administration. Gastrocnemius muscle UCPP gene expression was reduced in lean Trecadrine-treated and diet-induced obese animals as compared to controls, while an increase was found in cafeteria-fed animals after Trecadrine administration. A negative correlation between WAT O-2 consumption and UCPP expression was found in control animals, but not in the cafeteria-fed groups, suggesting a differential response to the beta(3)-adrenergic compound in lean and obese animals, which is in agreement with the reported statistical interactions between obesity and Trecadrine administration found for WAT O-2 consumption and muscle UCPP expression, as well as for plasma leptin and WAT leptin expression. CONCLUSION: The new beta(3)-adrenergic agonist, Trecadrine, decreases fat content and increases gastrocnemius muscle UCP2 gene expression in a diet-induced obesity model. This sheds additional light on the action mechanism of compounds with affinity for beta(3)-adrenoceptors and other potential anti-obesity agents.