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...

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Detalles Bibliográficos
Autores: Zhao, Wenli, Shen, Yuedong, Bao, Yangguang, Monroig, Óscar, Zhu, Tingting, Sun, Peng, Tocher, Douglas R., Zhou, Qicun, Jin, Min
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/373321
Acceso en línea:http://hdl.handle.net/10261/373321
Access Level:acceso abierto
Palabra clave:Fucoidan
Sirt1
Perk-Eif2α-Atf4 axis
Nuclear translocation
Lipid deposition
Descripción
Sumario: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.