Research ReportsFenofibrate ameliorates olanzapine’s side effects without altering its central effect: emphasis on FGF-21–adiponectin axisGalal, Ayaa; El-Bakly, Wesam M.b; El-Kilany, Sara S.c; Ali, Azza A.d; El-Demerdash, Ebtehale Author Information aCardiac Surgery Hospital, Ain Shams University bDepartment of Pharmacology cDepartment of Anatomy, Faculty of Medicine, Ain Shams University dDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar university (Girls Branch) eDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abbasia, Cairo, Egypt Received 18 December 2020 Accepted as revised 19 August 2021 Correspondence to Ebtehal El-Demerdash, PhD, Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain Shams University, Abbasia, Cairo, Egypt, Tel: +002 02 224729767, +002 01001925375; e-mail: [email protected] Behavioural Pharmacology: December 2021 - Volume 32 - Issue 8 - p 615-629 doi: 10.1097/FBP.0000000000000656 Buy Metrics Abstract The present work was designed to investigate whether fenofibrate could ameliorate olanzapine deleterious effect on insulin resistance via its effect on fibroblast growth factor-21 (FGF-21)–adiponectin axis without affecting olanzapine antipsychotic effect in postweaning socially isolated reared female rats. Treatment with olanzapine (6 mg/kg, intraperitoneally) or fenofibrate (100 mg/kg, orally) have been started 5 weeks after isolation, then behavioral tests, hippocampal content of neurotransmitters, and brain-derived neurotrophic factor (BDNF) were assessed. Moreover, insulin resistance, lipid profile, FGF-21, adiponectin, inflammatory, and oxidative stress markers of adipose tissue were assessed. Treatment of isolated-reared animals with olanzapine, or fenofibrate significantly ameliorated the behavioral and biochemical changes induced by postweaning social isolation. Co-treatment showed additive effects in improving hippocampal BDNF level. Besides, fenofibrate reduced the elevation in weight gain, adiposity index, insulin resistance, lipid profile, and FGF-21 level induced by olanzapine treatment. Also, fenofibrate increased adiponectin level which was reduced upon olanzapine treatment. Moreover, fenofibrate improved both adipose tissue oxidative stress and inflammatory markers elevation as a result of olanzapine treatment. Fenofibrate could ameliorate olanzapine-induced insulin resistance without affecting its central effect in isolated reared rats via its action on FGF-21–adiponectin axis. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.