title: Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats.
abstract: This study investigated the effects of rimonabant (SR141716), an antagonist of the cannabinoid receptor type 1 (CB1), on obesity-associated hepatic steatosis and related features of metabolic syndrome: inflammation (elevated plasma levels of tumor necrosis factor alpha [TNFalpha]), dyslipidemia, and reduced plasma levels of adiponectin. We report that oral treatment of obese (fa/fa) rats with rimonabant (30 mg/kg) daily for 8 weeks abolished hepatic steatosis. This treatment reduced hepatomegaly, reduced elevation of plasma levels of enzyme markers of hepatic damage (alanine aminotransferase, gamma glutamyltransferase, and alkaline phosphatase) and decreased the high level of local hepatic TNFalpha currently associated with steatohepatitis. In parallel, treatment of obese (fa/fa) rats with rimonabant reduced the high plasma level of the proinflammatory cytokine TNFalpha and increased the reduced plasma level of the anti-inflammatory hormone adiponectin. Finally, rimonabant treatment also improved dyslipidemia by both decreasing plasma levels of triglycerides, free fatty acids, and total cholesterol and increasing the HDLc/LDLc ratio. All the effects of rimonabant found in this study were not or only slightly observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with rimonabant compared to diet. These results demonstrate that rimonabant plays a hepatoprotective role and suggest that this CB1 receptor antagonist potentially has clinical applications in the treatment of obesity-associated liver diseases and related features of metabolic syndrome.
authors.affiliation: Sanofi-Aventis Recherche & Développement, Discovery Research CNS Department, Montpellier, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Gary-Bobo
authors.forename: Ghizlane
authors.initials: G
authors.lastname: Elachouri
authors.forename: Jean François
authors.initials: JF
authors.lastname: Gallas
authors.forename: Philip
authors.initials: P
authors.lastname: Janiak
authors.forename: Pietro
authors.initials: P
authors.lastname: Marini
authors.forename: Christine
authors.initials: C
authors.lastname: Ravinet-Trillou
authors.forename: Michèle
authors.initials: M
authors.lastname: Chabbert
authors.forename: Noël
authors.initials: N
authors.lastname: Cruccioli
authors.forename: Christian
authors.initials: C
authors.lastname: Pfersdorff
authors.forename: Claude
authors.initials: C
authors.lastname: Roque
authors.forename: Michèle
authors.initials: M
authors.lastname: Arnone
authors.forename: Tiziano
authors.initials: T
authors.lastname: Croci
authors.forename: Philippe
authors.initials: P
authors.lastname: Soubrié
authors.forename: Florence
authors.initials: F
authors.lastname: Oury-Donat
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Maffrand
authors.forename: Bernard
authors.initials: B
authors.lastname: Scatton
authors.forename: Frederic
authors.initials: F
authors.lastname: Lacheretz
authors.forename: Gérard
authors.initials: G
authors.lastname: Le Fur
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Herbert
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bensaid
mesh_terms: D000818:Animals; D063387:Cannabinoid Receptor Antagonists; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control*; D007249:Inflammation / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000517:prevention & control*; D009765:Obesity / Q000150:complications*; D010880:Piperidines / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077285:Rimonabant; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D000077285:Rimonabant