title: The elucidation of the mechanism of weight gain and glucose tolerance abnormalities induced by chlorpromazine.
abstract: Antipsychotic drugs induce weight gain and metabolic abnormalities. Recently, the role of adipocytokines secreted from adipocytes in the development of metabolic syndrome has received attention. The aim of this study was to investigate the effects of chlorpromazine (Cp) on body weight, glucose, lipid metabolism, and adipocytokine secretion in rats fed sucrose. Wistar rats received 15% sucrose (Suc group), 15% sucrose and Cp at 7.5 mg/kg per day (Suc + Cp group), or Cp alone (Cp group) in water for 10 weeks. Fasting glucose levels in the Suc and Suc + Cp groups were significantly higher than in the control (Cont) group. Fasting insulin levels in the Suc, Suc + Cp, and Cp groups were also significantly higher than in the Cont group. The adiponectin level in the Suc group was significantly higher than in the Cont group, although the adiponectin level in the Suc + Cp group was not. Furthermore, the plasma tumor necrosis factor (TNF)-alpha level in the Suc + Cp group was significantly higher than in the Suc group. These data suggest that Cp inhibits the compensatory response of adiponectin with respect to obesity due to increased expression of plasma TNF-alpha level. Cp may exert more harmful effects on the glucose level and insulin resistance than on other factors, which may be one of the mechanisms responsible for the metabolic syndrome induced by antipsychotic agents.
authors.affiliation: Department of Pharmacology, St. Marianna University School of Medicine, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Amamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumai
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakaya
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Tsuzuki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001786:Blood Glucose / Q000378:metabolism*; D002746:Chlorpromazine / Q000009:adverse effects*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D014150:Antipsychotic Agents; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D013395:Sucrose; D002746:Chlorpromazine