Sargassum fusiforme polysaccharide (SFP) is a kind of biologically active macromolecule with biological functions. In this study, oxidative stress and high‐fat HepG2 cell models were established to investigate its lipid‐lowering activity and mechanism of action. It was found that SFP and its two isolated fractions had antioxidant effects on the cells. It was also found the polysaccharides decreased the content of total cholesterol and total triglyceride in the high‐fat cells. RT‐qPCR assays revealed that the three polysaccharides down‐regulated the mRNA expression level of ACC, PPARγ, and SREBP‐2. It could be concluded that the hypolipidemic effect of SFPs is achieved via multiple pathways, including the regulation on the expression level of lipid metabolism‐related key enzymes and factors, and binding with bile acids. The hypolipidemic effect of SFPs could be partially due to their antioxidant activity. SFPs developed in the present work have potential as ingredients of functional foods with hypolipidemic effect.
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