title: Rimonabant ameliorates insulin resistance via both adiponectin-dependent and adiponectin-independent pathways.
abstract: Rimonabant has been shown to not only decrease the food intake and body weight but also to increase serum adiponectin levels. This increase of the serum adiponectin levels has been hypothesized to be related to the rimonabant-induced amelioration of insulin resistance linked to obesity, although experimental evidence to support this hypothesis is lacking. To test this hypothesis experimentally, we generated adiponectin knock-out (adipo(-/-))ob/ob mice. After 21 days of 30 mg/kg rimonabant, the body weight and food intake decreased to similar degrees in the ob/ob and adipo(-/-)ob/ob mice. Significant improvement of insulin resistance was observed in the ob/ob mice following rimonabant treatment, associated with significant up-regulation of the plasma adiponectin levels, in particular, of high molecular weight adiponectin. Amelioration of insulin resistance in the ob/ob mice was attributed to the decrease of glucose production and activation of AMP-activated protein kinase (AMPK) in the liver induced by rimonabant but not to increased glucose uptake by the skeletal muscle. Interestingly, the rimonabant-treated adipo(-/-)ob/ob mice also exhibited significant amelioration of insulin resistance, although the degree of improvement was significantly lower as compared with that in the ob/ob mice. The effects of rimonabant on the liver metabolism, namely decrease of glucose production and activation of AMPK, were also less pronounced in the adipo(-/-)ob/ob mice. Thus, it was concluded that rimonabant ameliorates insulin resistance via both adiponectin-dependent and adiponectin-independent pathways.
authors.affiliation: Department of Diabetes and Metabolic Diseases, University of Tokyo, Tokyo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Watanabe
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohsugi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kubota
authors.forename: Iseki
authors.initials: I
authors.lastname: Takamoto
authors.forename: Masato
authors.initials: M
authors.lastname: Iwabu
authors.forename: Motoharu
authors.initials: M
authors.lastname: Awazawa
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Katsuyama
authors.forename: Chiaki
authors.initials: C
authors.lastname: Hasegawa
authors.forename: Kumpei
authors.initials: K
authors.lastname: Tokuyama
authors.forename: Masao
authors.initials: M
authors.lastname: Moroi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugi
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Kohjiro
authors.initials: K
authors.lastname: Ueki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D000077285:Rimonabant
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D010880:Piperidines; D011720:Pyrazoles; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D000077285:Rimonabant