title: Olanzapine, but not aripiprazole, weight-independently elevates serum triglycerides and activates lipogenic gene expression in female rats.
abstract: Metabolic adverse effects such as weight gain and dyslipidaemia represent a major concern in treatment with several antipsychotic drugs, including olanzapine. It remains unclear whether such metabolic side-effects fully depend on appetite-stimulating actions, or whether some dysmetabolic features induced by antipsychotics may arise through direct perturbation of metabolic pathways in relevant peripheral tissues. Recent clinical and preclinical studies indicate that dyslipidaemia could occur independently of weight gain. Using a rat model, we showed that subchronic treatment with olanzapine induces weight gain and increases adipose tissue mass in rats with free access to food. This effect was also observed for aripiprazole, considered metabolically neutral in the clinical setting. In pair-fed rats with limited food access, neither olanzapine nor aripiprazole induced weight gain. Interestingly, olanzapine, but not aripiprazole, induced weight-independent elevation of serum triglycerides, accompanied by up-regulation of several genes involved in lipid biosynthesis, both in liver and in adipose tissues. Our findings support the existence of tissue-specific, weight-independent direct effects of olanzapine on lipid metabolism.
authors.affiliation: Dr. Einar Martens' Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Norway.
authors.forename: Silje
authors.initials: S
authors.lastname: Skrede
authors.forename: Johan
authors.initials: J
authors.lastname: Fernø
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Vázquez
authors.forename: Sveinung
authors.initials: S
authors.lastname: Fjær
authors.forename: Tina
authors.initials: T
authors.lastname: Pavlin
authors.forename: Niclas
authors.initials: N
authors.lastname: Lunder
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
authors.forename: Carlos
authors.initials: C
authors.lastname: Diéguez
authors.forename: Rolf Kristian
authors.initials: RK
authors.lastname: Berge
authors.forename: Miguel
authors.initials: M
authors.lastname: López
authors.forename: Vidar Martin
authors.initials: VM
authors.lastname: Steen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000633:toxicity; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D006963:Hyperphagia / Q000097:blood / Q000139:chemically induced; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects*; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology* / Q000633:toxicity; D015363:Quinolones / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D014280:Triglycerides; D001569:Benzodiazepines; D000068180:Aripiprazole; D000077152:Olanzapine