Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice

TLDR

The study examined whether the CB1 receptor antagonist SR141716 could reduce obesity in a diet‑induced obesity mouse model. SR141716 treatment for five weeks produced a 48 % drop in food intake in week 1, a sustained 20 % weight loss and 50 % reduction in adiposity, improved insulin sensitivity, lowered leptin, insulin, and free fatty acid levels, and these effects were dose‑dependent, absent in CB1‑knockout mice, indicating its potential as an anti‑obesity therapy.

Abstract

Because 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-wk treatment, SR141716 (10 mg · kg −1 · day −1 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 −1 · day −1 . 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 compared with vehicle-treated animals, and when a 3-day treatment was compared with 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.