POTENTIATION OF THE ANTIOBESITY EFFECT OF THE SELECTIVE BETA(3)-ADRENOCEPTOR AGONIST BRL-35135 IN OBESE ZUCKER RATS BY EXERCISE

1 The effects of chronic treatments with a selective beta(3)-adrenocep tor agonist and a selective cr,adrenoceptor antagonist and their inter actions with physical exercise training were studied in experimental o besity. 2 BRL 35135 (beta(3)-agonist, 0.5 mg kg(-1) day(-1) p.o.), ati pamezole (alpha(2)-antagonist, 4.0 mg kg(-1) day(-1) p.o.) and placebo were given to genetically obese male Zucker rats. Half of the rats we re kept sedentary whereas the other half were subjected to moderate tr eadmill exercise training. Body weight gain, cumulative food intake, t he neuropeptide Y content of the hypothalamic paraventricular nucleus, brown adipose tissue thermogenic activity (measured as GDP binding), plasma insulin and glucose levels were measured after 3 weeks' treatme nt and exercise. 3 Treatment with BRL 35135 reduced weight gain by 19% , increased brown adipose tissue thermogenic activity 45-fold and redu ced plasma insulin by 50%. Atipamezole slightly increased food intake and neuropeptide Y content in the paraventricular hypothalamic nucleus but had no effect on the other measured parameters. Exercise alone ha d no effect on weight gain, food intake or thermogenic activity, where as it reduced plasma insulin and glucose levels. 4 The effect of BRL 3 5135 on weight gain and thermogenic activity was significantly potenti ated by exercise; the reduction in weight gain was 56% in comparison w ith 19% in sedentary animals. Food intake was significantly reduced in the BRL 35135-treated-exercise-trained animals, although neither beta (3)-agonist nor exercise alone affected it. 5 Based on the present res ults in genetically obese Zucker rats, combination of beta(3)-agonist treatment with a moderate physical training may offer a new feasible a pproach to the therapy of obesity.