title: Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat.
abstract: OBJECTIVE
  This study aims to investigate whether orexigenic antipsychotic drugs may induce dyslipidemia and glucose disturbances in female rats through direct perturbation of metabolically active peripheral tissues, independent of prior weight gain.
  
  
  METHODS
  In the current study, we examined whether a single intraperitoneal injection of clozapine or olanzapine induced metabolic disturbances in adult female outbred Sprague-Dawley rats. Serum glucose and lipid parameters were measured during time-course experiments up to 48 h. Real-time quantitative PCR was used to measure specific transcriptional alterations in lipid and carbohydrate metabolism in adipose tissue depots or in the liver.
  
  
  RESULTS
  Our results demonstrated that acute administration of clozapine or olanzapine induced a rapid, robust elevation of free fatty acids and glucose in serum, followed by hepatic accumulation of lipids evident after 12-24 h. These metabolic disturbances were associated with biphasic patterns of gluconeogenic and lipid-related gene expression in the liver and in white adipose tissue depots.
  
  
  CONCLUSIONS
  Our results support that clozapine and olanzapine are associated with primary effects on carbohydrate and lipid metabolism associated with transcriptional changes in metabolically active peripheral tissues prior to the development of drug-induced weight gain.
authors: Dr. Einar Martens' Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Goran
authors: G
authors: Jassim
authors: Silje
authors: S
authors: Skrede
authors: María Jesús
authors: MJ
authors: Vázquez
authors: Hege
authors: H
authors: Wergedal
authors: Audun O
authors: AO
authors: Vik-Mo
authors: Niclas
authors: N
authors: Lunder
authors: Carlos
authors: C
authors: Diéguez
authors: Antonio
authors: A
authors: Vidal-Puig
authors: Rolf K
authors: RK
authors: Berge
authors: Miguel
authors: M
authors: López
authors: Vidar M
authors: VM
authors: Steen
authors: Johan
authors: J
authors: Fernø
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001569:Benzodiazepines / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D003024:Clozapine / Q000008:administration & dosage*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects*; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine