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Central Nervous System Research, Sanofi-Synthélabo, 31036 Toulouse Cedex, France
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 · day1
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 · kg1 · day1.
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.
endocannabinoid; body weight; food intake; insulin resistance; metabolic rate; CB1 receptor knockout mice
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