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Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice
Christine Ravinet Trillou1, Michele Arnone, Claire Delgorge
1Central Nervous System Research, Sanofi-Synthélabo, 31036 Toulouse Cedex, France. christine.ravinet-trillou@sanofi-synthelabo.com
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.
Insights
The CB1 receptor antagonist SR141716 significantly reduced body weight and adiposity in diet-induced obesity mice. This compound shows potential as a novel anti-obesity treatment by influencing metabolic processes.
Area of Science:
- Pharmacology
- Metabolic Disorders
- Obesity Research
Background:
- The CB1 receptor antagonist SR141716 is known to modulate food intake in rodents.
- Diet-induced obesity (DIO) models are widely used to study human obesity syndrome.
- Understanding mechanisms for obesity treatment is crucial.
Purpose of the Study:
- To investigate the efficacy of SR141716 in reducing obesity in a DIO mouse model.
- To explore the effects of SR141716 on food intake, body weight, adiposity, and metabolic parameters.
Main Methods:
- Administration of SR141716 (10 mg/kg/day and 3 mg/kg/day) orally to DIO mice for 5 weeks.
- Assessment of food intake, body weight, adiposity, insulin resistance, and plasma levels of leptin, insulin, and free fatty acids.
- Comparison of effects in CB1 receptor knockout mice and through pair-feeding studies.
Main Results:
- SR141716 (10 mg/kg/day) induced a transient reduction in food intake (-48% at week 1) and sustained reduction in body weight (-20%) and adiposity (-50%).
- The compound corrected insulin resistance and lowered plasma leptin, insulin, and free fatty acid levels.
- Effects were dose-dependent and confirmed to be CB1 receptor-mediated, as SR141716 had no effect in knockout mice.
Conclusions:
- SR141716 demonstrates significant potential as a novel anti-obesity treatment.
- The compound's efficacy extends beyond appetite suppression, influencing metabolic processes.
- Further research into SR141716 for obesity management is warranted.
