Anti-obesity 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-adrenergic agonists for the treatment and prevention of obesity in the dog. When a selective beta 3-adrenergic agonist, CL316,243 (0.1 mg/kg), was given orally to adult beagles every day for 5-7 weeks, body weight and girth were decreased compared with control placebo-treated dogs. Gross anatomical examinations revealed no noticeable abnormalities in CL316,243-treated dogs, except an apparent decrease in abdominal fat. Immunohistochemical examination of perirenal adipose tissue showed a remarkable increase in brown adipocytes expressing a thermogenic protein, uncoupling protein (UCP). The increased expression of UCP and its mRNA in CL316,243-treated dogs was also confirmed by Western blot and reverse transcription polymerase chain reaction analyses. It was concluded that treatment with a beta 3-adrenergic agonist stimulates UCP expression, which may lead to an increase in energy expenditure, and thereby is useful for the treatment and prevention of obesity in the dog.