Anti-Obesity Effects of Selective Agonists to the β3-Adrenergic Receptor in Dogs. II. Recruitment of Thermogenic Brown Adipocytes and Reduction of Adiposity after Chronic Treatment with a β3-Adrenergic Agonist

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The aim of this study was to evaluate the effectiveness of β3-adrenergic agonists for the treatment and prevention of obesity in the dog. When a selective β3-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 β3-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.