Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice.
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.
Ravinet Trillou
Christine
C
Central Nervous System Research, Sanofi-Synthélabo, 31036 Toulouse Cedex, France. christine.ravinet-trillou@sanofi-synthelabo.com
Arnone
Michele
M
Delgorge
Claire
C
Gonalons
Nadine
N
Keane
Peter
P
Maffrand
Jean-Pierre
JP
Soubrie
Philippe
P
D000818:Animals; D001665:Binding Sites; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000077285:Rimonabant; D013997:Time Factors
D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000077285:Rimonabant