title: Olanzapine-depot administration induces time-dependent changes in adipose tissue endocrine function in rats.
abstract: Metabolic adverse effects of atypical antipsychotics (AAP) contribute significantly to increased risk of cardiovascular morbidity and mortality in patients suffering from schizophrenia. Extensive preclinical research has addressed this issue over the past years, though mechanisms underlying these adverse effects of AAP are still not understood completely. Recently, attention is drawn towards the role of adipose tissue metabolism and neurohormonal regulations.
  
  
  
  The aim of this study was to evaluate the time-dependent effects of olanzapine depot administration at clinically relevant dosing on the regulation of energy homeostasis, glucose and lipid metabolism, gastrointestinal and adipose tissue-derived hormones involved in energy balance regulations in female Sprague-Dawley rats. The study lasted 8 weeks and the markers were assayed at day 8, 15, 29, 43 and 57.
  
  
  
  The results indicate that in the absence of hyperphagia, olanzapine chronic exposure induced weight gain from the beginning of the study. In the later time-point, increased adiposity was also observed. In the initial phase of the study, lipid profile was altered by an early increase in triglyceride level and highly elevated leptin level was observed. Clear bi-phasic time-dependent effect of olanzapine on leptin serum concentration was demonstrated. Olanzapine treatment did not lead to changes in serum levels of ghrelin, FGF-21 and pro-inflammatory markers IL-1a, IL-6 and TNF-α at any time-point of the study.
  
  
  
  This study provides data suggesting early alteration in adipose tissue endocrine function as a factor involved in mechanisms underlying metabolic adverse effects of antipsychotics.
authors: Department of Pharmacology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors: Katerina
authors: K
authors: Horska
authors: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. Electronic address: jkucer@med.muni.cz.
authors: Jana
authors: J
authors: Ruda-Kucerova
authors: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors: Zuzana
authors: Z
authors: Babinska
authors: R&D Department, Biovendor - Laboratorni Medicina, Brno, Czech Republic; Department of Pharmacology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors: Michal
authors: M
authors: Karpisek
authors: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors: Regina
authors: R
authors: Demlova
authors: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors: Radka
authors: R
authors: Opatrilova
authors: Department of Pharmacology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors: Pavel
authors: P
authors: Suchy
authors: Department of Pharmacology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors: Hana
authors: H
authors: Kotolova
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood / Q000378:metabolism*; D005260:Female; D020738:Leptin / Q000097:blood*; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood*; D015430:Weight Gain
chemical_list: D014150:Antipsychotic Agents; D020738:Leptin; D014280:Triglycerides; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: Adipokine; Adipose tissue; Dyslipidemia; Leptin; Olanzapine; Sprague-Dawley rats