AUTHOR=Hu Mengyao , Chen Yu , Deng Fan , Chang Bo , Luo Jialiang , Dong Lijun , Lu Xiao , Zhang Yi , Chen Zhengliang , Zhou Jia 

TITLE=D-Mannose Regulates Hepatocyte Lipid Metabolism via PI3K/Akt/mTOR Signaling Pathway and Ameliorates Hepatic Steatosis in Alcoholic Liver Disease

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.877650

DOI=10.3389/fimmu.2022.877650

ISSN=1664-3224

ABSTRACT=<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 (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 <italic>via</italic> PI3K/Akt/mTOR signaling pathway.</p>