Fucoidan alleviates hepatic lipid deposition by modulating the Perk-Eif2α-Atf4 axis via Sirt1 activation in Acanthopagrus schlegelii

With the increasing use of high-fat diets (HFD), fatty liver disease has become common in fish, and fucoidan is of interest as a natural sulfated polysaccharide with lipid-lowering activity. To explore the molecular regulatory mechanisms of fucoidan's alleviation of HFD-induced lipid deposition in liver, black seabream (Acanthopagrus schlegelii) was used to construct in vivo and in vitro HFD models. In vivo HFD stimulated the protein kinase RNAlike endoplasmic reticulum kinase (Perk) pathway, and up-regulated proliferator-activated receptor gamma (Ppar gamma) nuclear translocation and expression of lipogenic genes, while it down-regulated Ppar alpha (Ppar alpha) nuclear translocation and expression of lipolytic genes. However, fucoidan reversed these effects of HFD and significantly alleviated HFD-induced lipid accumulation in liver. Moreover, after sirtuin 1 (sirt1) knockdown, these effects of fucoidan disappeared. In the in vitro HFD model, GSK2606414 (GSK)-specific inhibition of the Perk pathway, decreased Ppar gamma nuclear translocation and increased Ppar alpha nuclear translocation. Overall, fucoidan mitigated HFD-induced, Perk pathway-mediated lipid deposition in the liver of black seabream by activating Sirt1. The findings provided a new prospect for the application of green polysaccharides in aquatic animal feeds.