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 O2 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 UCP2 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 O2 consumption and UCP2 expression was found in control animals, but not in the cafeteria-fed groups, suggesting a differential response to the beta3-adrenergic compound in lean and obese animals, which is in agreement with the reported statistical interactions between
obesity and
Trecadrine administration found for WAT O2 consumption and muscle UCP2 expression, as well as for plasma
leptin and WAT
leptin expression.
CONCLUSION: The new beta3-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 beta3-adrenoceptors and other potential
anti-obesity agents.