Saikosaponin d alleviates high-fat-diet induced hepatic steatosis in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀) by targeting AMPK/PPARα pathway

Abstract

High-fat diets generally cause the accumulation of hepatic steatosis in farmed fish tissues, which results in metabolic disorders, abnormal oxidative status and immune system suppression, seriously affecting sustainable aquaculture development. The main bioactive components of Bupleurum are saikosaponins, saikosaponins d (SSd) exhibiting the strongest pharmacological activity. The aim of this research was to examine the preventive and therapeutic benefits of SSd on hepatic steatosis, in addition to the underlying processes of hybrid groupers in vitro and in vivo. SSd was found to enhance cell survival in vitro by lowering apoptosis and decrease lipid accumulation in hepatocytes by reducing oxidative stress, restricting lipogenesis and enhancing lipid oxidation. In vivo, 300 hybrid groupers were fed SSd at dosages of 0, 100, 200, 400, and 800 mg/kg that was supplemented with a high-lipid basal diet for eight weeks. Pretreatment with SSd caused a raised expression in lipolysis-related genes (AMPKα, PPARα, CPT1, LPL) while decreasing the expression of adipogenesis-related genes in the liver of hybrid groupers (G6PD, ME1, FAS and DGAT2). Furthermore, kinsenoside was found to increase ATGL-mediated lipolysis, amplified by AMP-activated protein kinase (AMPK) activation, in addition to the hydrolysis of triglycerides to glycerol and fatty acids, which require transit into mitochondria for further oxidation. AMPK activation was found to increase ATGL expression for lipolysis, while also increasing CPT1 expression for fatty acid transport to the mitochondria. The findings of this study add to a growing body of evidence suggesting SSd therapy can be used for the prevention hepatic steatosis in hybrid groupers via the AMPK/PPAR pathway.