DataSheet_1_D-Mannose Regulates Hepatocyte Lipid Metabolism via PI3K/Akt/mTOR Signaling Pathway and Ameliorates Hepatic Steatosis in Alcoholic Liver Disease.pdf

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 (PPARα, 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 via PI3K/Akt/mTOR signaling pathway.

本研究探究了D-甘露糖（D-mannose）对实验性酒精性肝病（ALD）中肝脂肪变性的保护作用及其机制。通过在饮用水中添加D-甘露糖，可显著减轻慢性-间歇乙醇喂养构建的标准小鼠ALD模型中的肝脂肪变性，尤其是肝细胞脂质沉积情况。该D-甘露糖对肝细胞脂质蓄积的调控作用，在添加了D-甘露糖的乙醇处理原代小鼠肝细胞（PMHs）模型中也得到了验证。与此同时，D-甘露糖可通过逆转乙醇介导的脂肪酸氧化相关基因（PPARα、ACOX1、CPT1）表达下调，以及脂肪生成相关基因（SREBP1c、ACC1、FASN）表达上调，来调控脂质代谢。PI3K/Akt/mTOR信号通路参与了D-甘露糖对脂质代谢的调控作用，因为在PMHs中，PI3K/Akt/mTOR通路的抑制剂或激动剂均可抵消该调控效果。综上，本研究结果表明，D-甘露糖可通过PI3K/Akt/mTOR信号通路调控肝细胞脂质代谢，从而在ALD中发挥抗脂肪变性的作用。