Rice Protein Peptides\nAlleviate Alcoholic Liver Disease\nvia the PPARγ Signaling Pathway: Through Liver Metabolomics\nand Gut Microbiota Analysis

Alcoholic liver disease (ALD) is the predominant type\nof liver\ndisease worldwide, resulting in significant mortality and a high disease\nburden. ALD damages multiple organs, including the liver, gut, and\nbrain, causing inflammation, oxidative stress, and fat deposition.\nIn this study, we investigated the effects of rice protein peptides\n(RPP) on ALD in mice with a primary focus on the gut microbiota and\nliver metabolites. The results showed that administration of RPP significantly\nalleviated the symptoms of ALD in mice including adiposity, oxidative\nstress, and inflammation. The KEGG pathway shows that RPP downregulates\nthe liver metabolite of capric acid and the metabolism of fatty acid\nbiosynthesis compared with the MOD group. Mechanistically, RPP downregulated\nthe PPARγ signaling pathway and suppressed the expression of\nfatty acid biosynthesis genes (FASN, ACC1, ACSL1, and ACSL3). Furthermore,\ntwo active peptides (YLPTKQ and PKLPR) with potential therapeutic\nfunctions for ALD were screened by Caco-2 cell modeling and molecular\ndocking techniques. In addition, RPP treatment alleviates gut microbiota\ndysbiosis by reversing the F/B ratio, increasing the relative abundance\nof <i>Alloprevotella</i> and <i>Alistipes</i>,\nand upregulating the level of short-chain fatty acids. In conclusion,\nRPP alleviates ALD steatosis through the PPARγ signaling pathway\nby YLPTKQ and PKLPR and regulates gut microbiota.