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Currently, there is a lack of intervention or therapeutic drugs against NAFLD. In this study, we investigated the ability of <jats:italic>Sargassum fusiforme<\/jats:italic> polysaccharide (SFPS) to reduce lipid accumulation induced by high sugar in HepG2 cells and <jats:italic>Drosophila melanogaster<\/jats:italic> larvae. The results indicated that SFPS significantly (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01) decreased the accumulation of lipid droplets in high sugar\u2013induced HepG2 cells. Furthermore, SFPS also suppressed the expression of <jats:italic>Srebp<\/jats:italic> and <jats:italic>Fas<\/jats:italic> (genes involved in lipogenesis) and increased the expression of <jats:italic>PPAR\u0251<\/jats:italic> and <jats:italic>Cpt1<\/jats:italic> (genes that participated in fatty acid \u03b2\u2010oxidation) in these cells. SFPS markedly reduced the content of triglyceride of the third instar larvae developed from <jats:italic>D.\u00a0melanogaster<\/jats:italic> eggs reared on the high\u2010sucrose diet. The expression of the <jats:italic>Srebp<\/jats:italic> and <jats:italic>Fas<\/jats:italic> genes in the larvae was also inhibited whereas the expression of two genes involved in the \u03b2\u2010oxidation of fatty acids, <jats:italic>Acox57D\u2010d<\/jats:italic> and <jats:italic>Fabp,<\/jats:italic> was increased in the larval fat body (a functional homolog of the human liver). We also found that SFPS ameliorated developmental abnormalities induced by the high\u2010sucrose diet. These results of this study suggest that SFPS could potentially be used as a therapeutic agent for the prevention and treatment of NAFLD.<\/jats:p>","DOI":"10.1002\/fsn3.2521","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T08:40:18Z","timestamp":1628757618000},"page":"5590-5599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<i>Sargassum fusiforme<\/i> polysaccharide attenuates high\u2010sugar\u2013induced lipid accumulation in HepG2 cells and <i>Drosophila melanogaster<\/i> larvae"],"prefix":"10.1002","volume":"9","author":[{"given":"Dan","family":"He","sequence":"first","affiliation":[{"name":"College of Life and Environmental Science Wenzhou University Wenzhou China"},{"name":"Department of Biotechnology and Bioengineering Chonnam National University Gwangju South 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