The Roles And Interaction Of Fxr And Ppars In The Pathogenesis Of Nonalcoholic Fatty Liver Disease

Background and study aims: To identify the roles and interaction of farnesoid X receptor (FXR) and peroxisome proliferator activated receptors (PPARs) in Non-alcoholic fatty liver disease (NAFLD) pathogenesis.Material and Methods: 16 C57/BL male FXR knockout (KO) mice and sex- and age-matched C57/BL wild type mice were received either standard rodent chow or high-fat and sucrose diet (Blank control, NAFLD, FXR KO and FXR KO NAFLD) for 8 weeks. After that, all mice were sacrificed. Liver tissues and blood samples were collected for laboratory and RT-PCR examination.Results: NAFLD, FXR KO and FXR KO NAFLD mouse models were successful established. Compared with blank control, FXR and PPAR-alpha mRNA expression decreased significantly (P < 0.05), PPAR-beta expression increased slightly (P > 0.05), PPAR-gamma expression increased significantly in NAFLD (P < 0.05). Slight increased PPAR-alpha mRNA expression (P > 0.05) and markedly decreased APAR-beta and PPAR-gamma expression (P < 0.05) were found in FXR KO. Compared with FXR KO group, there was a slight increase in APAR-alpha and PPAR-beta mRNA expression (P > 0.05) and significant increase in PPAR-gamma expression (P < 0.05) in FXR KO NAFLD group. Comparison with NAFLD, PPAR-alpha mRNA expression increased slightly (P > 0.05), APAR-beta and PPAR-gamma expression decreased significantly (P < 0.05) in FXR KO NAFLD.Conclusion: FXR and PPARs interaction may play important roles in NAFLD pathogenesis. (C) 2020 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.