Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat

• Published in: Psychopharmacologia 2012-02, Vol.219 (3), p.783-794
• Main Authors: Jassim, Goran, Skrede, Silje, Vázquez, María Jesús, Wergedal, Hege, Vik-Mo, Audun O., Lunder, Niclas, Diéguez, Carlos, Vidal-Puig, Antonio, Berge, Rolf K., López, Miguel, Steen, Vidar M., Fernø, Johan
• Format: Article
• Language: English
• Subjects: Acute effects; Adipose tissue; Adipose tissues; Animals; Antipsychotic Agents - administration & dosage; Benzodiazepines - administration & dosage; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood Glucose - drug effects; Carbohydrate metabolism; Carbohydrate Metabolism - drug effects; Carbohydrates; Cholesterol; Clozapine; Clozapine - administration & dosage; Dextrose; Diabetes; Diabetes. Impaired glucose tolerance; Drug therapy; Dyslipidemia; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acids; Fatty Acids, Nonesterified - blood; Female; Gene expression; Glucose; Glucose metabolism; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Liver; Medical sciences; Metabolic diseases; Metabolism; Neuroleptics; Neuropharmacology; Neurosciences; Obesity; Olanzapine; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Polymerase chain reaction; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Rodents; Time Factors; Transcription; Weight Gain - drug effects
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-011-2397-y

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. Conclusion 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.