ANTIOBESITY EFFECTS OF SELECTIVE AGONISTS TO THE BETA-3-ADRENERGIC RECEPTOR IN DOGS - II - RECRUITMENT OF THERMOGENIC BROWN ADIPOCYTES AND REDUCTION OF ADIPOSITY AFTER CHRONIC TREATMENT WITH A BETA-3-ADRENERGIC AGONIST

The aim of this study was to evaluate the effectiveness of beta 3-adre nergic agonists for the treatment and prevention of obesity in the dog . When a selective beta 3-adrenergic agonist, CL316,243 (0.1 mg/kg), w as given orally to adult beagles every day for 5-7:weeks, body weight and girth were decreased compared with control placebo-treated dogs. G ross anatomical examinations revealed no noticeable abnormalities in C L316,243-treated dogs, except an apparent decrease in abdominal fat. I mmunohistochemical examination of perirenal adipose tissue showed a re markable increase in brown adipocytes expressing a thermogenic protein , uncoupling protein (UCP). The increased expression of UCP and its mR NA in CL316,243-treated dogs was also confirmed by Western blot and re verse transcription polymerase chain reaction analyses. It was conclud ed that treatment with a beta 3-adrenergic agonist stimulates UCP expr ession, which may lead to an increase in energy expenditure, and there by is useful for the treatment and prevention of obesity in the dog.