Potentiation of the anti-obesity 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-adrenoceptor agonist and a selective alpha 2-adrenoceptor antagonist and their interactions with physical exercise training were studied in experimental obesity. 2. BRL 35135 (beta 3-agonist, 0.5 mg kg-1 day-1 p.o.), atipamezole (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 were kept sedentary whereas the other half were subjected to moderate treadmill exercise training. Body weight gain, cumulative food intake, the 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' treatment and exercise. 3. Treatment with BRL 35135 reduced weight gain by 19%, increased brown adipose tissue thermogenic activity 45-fold and reduced 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 had no effect on weight gain, food intake or thermogenic activity, whereas it reduced plasma insulin and glucose levels. 4. The effect of BRL 35135 on weight gain and thermogenic activity was significantly potentiated by exercise; the reduction in weight gain was 56% in comparison with 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 results in genetically obese Zucker rats, combination of 03-agonist treatment with a moderate physical training may offer a new feasible approach to the therapy of obesity.-


BACKGROUND
BRL 35135; atipamezole; P3-adrenoceptor agonism; M2-adrenoceptor antagonism; brown adipose tissue; thermogenesis;genetic obesity; Zucker rat; exercise; neuropeptide Y
Santti
E
E
Department of Pharmacology, University of Turku, Finland.
Huupponen
R
R
Rouru
J
J
Hänninen
V
V
Pesonen
U
U
Jhanwar-Uniyal
M
M
Koulu
M
M
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001833:Body Temperature Regulation / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006153:Guanosine Diphosphate / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000523:psychology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D010805:Physical Conditioning, Animal; D051381:Rats; D011924:Rats, Zucker; D015430:Weight Gain / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D009478:Neuropeptide Y; D010627:Phenethylamines; C050701:atipamezole; D006153:Guanosine Diphosphate; C063157:BRL 35135