What question did this study set out to answer?

This research aims to explore how fucoxanthin impacts hepatic steatosis and ER stress by targeting GRP78.

May 6, 2026Open Access

Fucoxanthin Ameliorates MASLD by Directly Targeting GRP78 to Restore ER Homeostasis and Activate AMPK Signaling

Key Points

This research aims to explore how fucoxanthin impacts hepatic steatosis and ER stress by targeting GRP78.
Utilized mice and palmitic acid-induced HepG2 cells to test the effects of fucoxanthin.
Investigated the interaction between fucoxanthin and GRP78, as well as its impact on AMPK activation.
Conducted siRNA-mediated GRP78 knockdown and pharmacological AMPK inhibition to confirm the mechanistic pathway.
Fucoxanthin treatment significantly alleviated hepatic steatosis in experimental models.
Suppression of ER stress was observed alongside the activation of AMPK signaling.
The lipid-lowering and ER stress-relieving effects of fucoxanthin were abolished by GRP78 knockdown or AMPK inhibition.

Abstract

mice and palmitic acid-induced HepG2 cells, fucoxanthin treatment significantly alleviated hepatic steatosis and suppressed ER stress. Mechanistically, the fucoxanthin-GRP78 interaction was found to be indispensable for the subsequent activation of AMP-activated protein kinase (AMPK) signaling. Notably, siRNA-mediated knockdown of GRP78 or pharmacological inhibition of AMPK completely abolished the lipid-lowering and ER stress-relieving effects of fucoxanthin, confirming a causal GRP78-AMPK axis. This study elucidates a novel target-driven mechanism wherein fucoxanthin acts as a GRP78 ligand to restore ER homeostasis and reprogram lipid metabolism. These findings position the fucoxanthin-GRP78 axis as a specific therapeutic target for nutritional strategies against MASLD.

Fucoxanthin Ameliorates MASLD by Directly Targeting GRP78 to Restore ER Homeostasis and Activate AMPK Signaling

Key Points

Abstract

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