¹Department of Physiology and Nutrition, University of Navarra, 31008 Pamplona (Navarra), Spain

²Molecular Physiology Group, Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, Scotland, UK

Correspondence to: J A Martínez, Department of Physiology and Nutrition, University of Navarra, 31008 Pamplona, Spain. Jalfmtz@unav.es.

OBJECTIVE: The anti-obesity properties of a new 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 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 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 O₂ consumption and muscle UCP2 expression, as well as for plasma leptin and WAT leptin expression.

CONCLUSION: The new 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 ₃-adrenoceptors and other potential anti-obesity agents.

International Journal of Obesity (2000) 24, 156-163

obesity; ₃-adrenergic agonists; leptin; UCPs