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

Wenli Zhao; Yuedong Shen; Yangguang Bao; Óscar Monroig; Tingting Zhu; Peng Sun; Douglas R Tocher; Qicun Zhou; Min Jin

doi:10.1016/j.ijbiomac.2024.137266

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

Int J Biol Macromol. 2024 Nov 4:137266. doi: 10.1016/j.ijbiomac.2024.137266. Online ahead of print.

Authors

Wenli Zhao¹, Yuedong Shen¹, Yangguang Bao¹, Óscar Monroig², Tingting Zhu¹, Peng Sun¹, Douglas R Tocher³, Qicun Zhou¹, Min Jin⁴

Affiliations

¹ Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China; Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China; Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China.
² Instituto de Acuicultura Torre de la Sal (IATS), CSIC, 12595 Ribera de Cabanes, Castellon, Spain.
³ Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University, Shantou 515063, China.
⁴ Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, China; Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo 315211, China; Key Laboratory of Green Mariculture (Co-construction by Ministry and Province), Ministry of Agriculture and Rural, Ningbo University, Ningbo 315211, China. Electronic address: jinmin@nbu.edu.cn.

PMID: 39505163
DOI: 10.1016/j.ijbiomac.2024.137266

Abstract

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 RNA-like endoplasmic reticulum kinase (Perk) pathway, and up-regulated proliferator-activated receptor gamma (Pparγ) nuclear translocation and expression of lipogenic genes, while it down-regulated Ppar alpha (Pparα) 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 Pparγ nuclear translocation and increased Pparα 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.

Keywords: Fucoidan; Lipid deposition; Nuclear translocation; Perk-Eif2α-Atf4 axis; Sirt1.