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Immunol."],"abstract":"<jats:p>This study investigated the protective properties and mechanisms of D-mannose against hepatic steatosis in experimental alcoholic liver disease (ALD). Drinking-water supplementation of D-mannose significantly attenuated hepatic steatosis in a standard mouse ALD model established by chronic-binge ethanol feeding, especially hepatocyte lipid deposition. This function of D-mannose on lipid accumulation in hepatocytes was also confirmed using ethanol-treated primary mouse hepatocytes (PMHs) with a D-mannose supplement. Meanwhile, D-mannose regulated lipid metabolism by rescuing ethanol-mediated reduction of fatty acid oxidation genes (PPAR\u03b1, ACOX1, CPT1) and elevation of lipogenic genes (SREBP1c, ACC1, FASN). PI3K\/Akt\/mTOR signaling pathway was involved in this effect of D-mannose on lipid metabolism since PI3K\/Akt\/mTOR pathway inhibitors or agonists could abolish this effect in PMHs. Overall, our findings suggest that D-mannose exhibits its anti-steatosis effect in ALD by regulating hepatocyte lipid metabolism <jats:italic>via<\/jats:italic> PI3K\/Akt\/mTOR signaling pathway.<\/jats:p>","DOI":"10.3389\/fimmu.2022.877650","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T06:15:58Z","timestamp":1649312158000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["D-Mannose Regulates Hepatocyte Lipid Metabolism via PI3K\/Akt\/mTOR Signaling Pathway and Ameliorates Hepatic Steatosis in Alcoholic Liver 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