Effects of PPARα pathway on hepatic lipid metabolism in non-alcoholic fatty liver disease rat model

Abstract

Background Non-alcoholic fatty liver disease (NAFLD) is a common hepatic metabolic disorder that is characterized by the dyshomeostasis of lipid metabolism. It is usually accompanied by insulin resistance and hyperlipidemia. Regulating lipid metabolism via the peroxisome proliferator-activated receptor alpha (PPARα) pathway in the liver could potentially constitute a new target for elucidating the pathology of NAFLD. Therefore, we aimed to explore the PPARα pathway in a high-fat diet (HFD)-induced NAFLD rat model by non-competitive inhibitor MK886. Method Male Wistar rats were randomly divided into control (CON), HFD, HFD + MK 886 groups. After 14 weeks of intervention, body weight, energy intake, liver weight, serum biochemical markers, histology, morphology, and protein expression of PPARα, CPT1A, CD36, FABP1 in the liver were detected. Results Inhibiting PPARα by MK886 significantly reduced body weight; it improved hepatic function and serum lipid parameters. Furthermore, MK886 ameliorated hepatic steatosis by reducing the levels of CD36, PPARα and CPT1A. Conclusion The study indicates that inhibiting PPARα pathway could improve hepatic homeostasis by improving liver function and alleviating hepatic steatosis; this validated the role of PPARα and its downstream protein in hepatic fatty acid metabolism in NAFLD.