Selenium reduces hepatopancreas lipid accumulation of grass carp (Ctenopharyngodon idella) fed high-fat diet via lipophagy activation.

It has been reported that selenium (Se) can reduce hepatopancreas lipid accumulation induced by high-fat diet. However, its mechanism is still unknown. This study aims to investigate the specific mechanisms by which Se alleviates high-fat diet-induced lipid accumulation. Grass carp were fed control diet (4.8% lipid, Con), high-fat diet (8.8% lipid, HFD) or HFD supplemented with 0.3 mg/kg nano-Se (HSe0.3) for 10 weeks. Growth performance, Se deposition, lipid accumulation, hepatic ultrastructure, and gene and protein expression levels associated with autophagy were examined. Furthermore, oleic acid (OA) was used to incubate the grass carp hepatocytes (L8824) for 24 h, and then the L8824 were incubated with sodium selenite in presence or absence of an autophagy inhibitor for 24 h. L8824 was analyzed for triglyceride concentration, immunofluorescence, and gene and protein expression levels associated with autophagy. We found that dietary nano-Se improved the growth of fish fed HFD and also decreased hepatosomatic index and intraperitoneal fat ratio of fish fed HFD (P < 0.05). HFD significantly increased hepatopancreas lipid accumulation and decreased autophagic activity (P < 0.05). Treatment of grass carp fed HFD with nano-Se decreased lipid accumulation and restored hepatic autophagy (P < 0.05). In vitro, Se (100 μM sodium selenite) obviously activated autophagy in L8824 incubated with OA, and consequently reduced the lipid accumulation induced by OA (P < 0.05). Furthermore, using pharmacological inhibition (chloroquine) of the autophagy greatly diminished the beneficial effects of Se on alleviating OA-induced lipid accumulation and increased the co-localization of lipid droplets with autophagosome (P < 0.05), which indicated that Se increased autophagic flux. In conclusion, these results suggest that Se alleviates HFD-induced hepatopancreas lipid accumulation by activating lipophagy.