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...
| Autores: | , , , , , , , , |
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| 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 |
| 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. |
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