Effects of MK886 on hepatic lipid metabolism in non-alcoholic fatty liver disease

Abstract

Backgound 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 inhibitory role of MK886 through PPARα pathway in a high-fat diet (HFD)-induced NAFLD model. Method Male Wistar rats were randomly divided into control (CON), HFD, HFD + MK 886 groups. After 14 weeks of intervention, we evaluated body weight, energy intake, liver weight, serum inflammatory parameters, serum biochemical markers, histology, morphology, and lipid metabolism-associated proteins in the liver. Results MK886 significantly reduced body weight; it improved hepatic function, inflammatory cytokine levels, and serum lipid parameters. Furthermore, MK886 ameliorated hepatic steatosis by reducing the levels of lipid uptake-related proteins and β-oxidation-related proteins. Conclusion Our study indicates that MK886 could improve hepatic homeostasis by improving liver function and alleviating systemic inflammation and hepatic steatosis; this provides a basis for future drug development and future clinical trials.