New anti-obesity and anti-diabetic druges for dogs activating brown adipose tissue thermogenesis.

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Obesity is one of the most important risk factors for diabetes and hypertension in the dog, as in man. In this study, to explore an effective pharmacological method for treatment and prevention of obesity in small animal practises, we have examined in dogs anti-obesity effects of an agonist (CL316,243) to beta3-adrenoceptor which activates brown adipose tissue thermogenesis. When CL316,243 was given intravenously to Beagle dogs, plasma free fatty acid level increased promptly and remarakably, indicating a strong lipolytic action of this drug. When the drug was given orally for 5 weeks, body weight and girth length decreased significantly compared with placebo- controls. Biochemical and histological examinations revealed that the adipose tissues of the dogs chronically given the drug had less triglyceride and expressed a specific thermogenic protein (mitochondrial uncoupling protein). These results show that the beta3-adrenocetor agonist has potent lipolytic and thermogenic action and can be used as an anti-obesity drug in the dog.