Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver diseases. This study sought to evaluate the insulin-sensitizing effect of paeoniflorin (PF) on high-fat diet-induced NAFLD and possible molecular mechanisms. Male Sprague Dawley rats were fed a high-fat diet (HFD) for 10 weeks to establish the NAFLD model, and PF (20 mg/kg/d) was gavaged to the NAFLD rats for another four weeks. Our results demonstrated that HFD resulted in hepatocellular ballooning, micro-/macrovesicular steatosis, and oxidative stress in the liver, accompanied by increased serum total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and homeostasis model of insulin resistance (HOMA-IR) index. PF treatment improved the biochemical and histopathological changes in NAFLD rats. Moreover, we also found that PF could inhibit lipid ectopic deposition via regulating lipid metabolism (inhibiting lipid synthesis of cholesterol and de novo pathway), and exert insulin sensitizing effect by regulating the insulin signaling pathway IRS/Akt/GSK3β and anti-oxidation. The study findings suggest that PF has therapeutic potential against NAFLD and that it acts through multiple signaling pathways.
Highlights
It is widely accepted that the hepatic lipid accumulation of Non-alcoholic fatty liver disease (NAFLD) represents hepatic manifestations of impaired systemic insulin network[15]
We explored the effects of PF on improving fatty liver and insulin resistance (IR) in NAFLD rats based on its effects on the lipid metabolism-associated regulators and insulin-associated insulin receptor substrate (IRS)/Akt/GSK3βpathway
Our data suggest that PF could exert beneficial effects on NAFLD, in part, through regulating lipid metabolism, inhibiting oxidative stress and by regulating the IRS/Akt/GSK3βpathway
Summary
It is widely accepted that the hepatic lipid accumulation of NAFLD represents hepatic manifestations of impaired systemic insulin network[15]. One cause of IR in NAFLD is mediated by impaired insulin signaling pathway, for example, impairment of the insulin receptor substrate (IRS)-1/Akt/glycogen synthase kinase (GSK) 3βpathway[6]. Serine/threonine phosphorylation of IRS is associated with IR, and it is enhanced by elevated reactive oxygen species (ROS) levels and/or multiple inflammatory cytokines such as tumor necrosis factor (TNF) α16. Elevation of hepatic ROS levels has been proposed as a link between elevated serum free fatty acids www.nature.com/scientificreports/. We hypothesized that PF could suppress hepatic oxidative stress and restore the impaired IRS1/Akt/GSK3βsignaling pathway, leading to an improvement in IR. We evaluated the insulin-sensitizing effects of PF in a NAFLD rat model and explored its possible therapeutic mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
