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Articles in PresS, published online ahead of print October 24, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00545.2002
Submitted on September 6, 2002
Accepted on October 17, 2002
* To whom correspondence should be addressed. E-mail: christine.ravinet-trillou{at}sanofi-synthelabo.com.
As the CB1 receptor antagonist SR141716 was previously reported to modulate food intake in rodents, we studied its efficacy in reducing obesity in a diet-induced obesity (DIO) model widely used for research on the human obesity syndrome. During a 5-week treatment, SR141716 (10 mg/kg/d, orally) induced a transient reduction of food intake (-48% on week 1), and a marked but sustained reduction of body weight (-20%) and adiposity (-50%) of DIO mice. Furthermore, SR141716 corrected the insulin resistance and lowered plasma leptin, insulin and free fatty acid levels. Most of these effects were present but less pronounced at 3 mg/kg/d. In addition to its hypophagic action, SR141716 may influence metabolic processes as the body weight loss of SR141716-treated mice was significantly higher during 24-h fasting when compared to vehicle-treated animals, and when a 3-day treatment was compared to a pair-feeding. SR141716 had no effect in CB1 receptor knockout mice, which confirmed the implication of CB1 receptors in the activity of the compound. These findings suggest that SR141716 has a potential as a novel anti-obesity treatment.
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