State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China.
Jiangxi Medicine Academy of Nutrition and Health Management, Nanchang, Jiangxi 330052, China.
J Agric Food Chem. 2024 Oct 30;72(43):23790-23803. doi: 10.1021/acs.jafc.4c02671. Epub 2024 Oct 15.
Alcoholic liver disease (ALD) is the predominant type of liver disease worldwide, resulting in significant mortality and a high disease burden. ALD damages multiple organs, including the liver, gut, and brain, causing inflammation, oxidative stress, and fat deposition. In this study, we investigated the effects of rice protein peptides (RPP) on ALD in mice with a primary focus on the gut microbiota and liver metabolites. The results showed that administration of RPP significantly alleviated the symptoms of ALD in mice including adiposity, oxidative stress, and inflammation. The KEGG pathway shows that RPP downregulates the liver metabolite of capric acid and the metabolism of fatty acid biosynthesis compared with the MOD group. Mechanistically, RPP downregulated the PPARγ signaling pathway and suppressed the expression of fatty acid biosynthesis genes (FASN, ACC1, ACSL1, and ACSL3). Furthermore, two active peptides (YLPTKQ and PKLPR) with potential therapeutic functions for ALD were screened by Caco-2 cell modeling and molecular docking techniques. In addition, RPP treatment alleviates gut microbiota dysbiosis by reversing the F/B ratio, increasing the relative abundance of and , and upregulating the level of short-chain fatty acids. In conclusion, RPP alleviates ALD steatosis through the PPARγ signaling pathway by YLPTKQ and PKLPR and regulates gut microbiota.
酒精性肝病（ALD）是全球主要的肝脏疾病类型，导致高死亡率和高疾病负担。ALD 损伤多个器官，包括肝脏、肠道和大脑，引起炎症、氧化应激和脂肪沉积。在这项研究中，我们研究了大米蛋白肽（RPP）对小鼠 ALD 的影响，主要关注肠道微生物群和肝脏代谢物。结果表明，RPP 给药可显著缓解小鼠的 ALD 症状，包括肥胖、氧化应激和炎症。KEGG 途径显示，与 MOD 组相比，RPP 下调了肝脏代谢物辛酸和脂肪酸生物合成的代谢。在机制上，RPP 下调了 PPARγ 信号通路，并抑制了脂肪酸生物合成基因（FASN、ACC1、ACSL1 和 ACSL3）的表达。此外，通过 Caco-2 细胞建模和分子对接技术筛选出两种具有潜在治疗 ALD 作用的活性肽（YLPTKQ 和 PKLPR）。此外，RPP 通过逆转 F/B 比、增加和的相对丰度以及上调短链脂肪酸水平来缓解肠道微生物群失调。总之，RPP 通过 YLPTKQ 和 PKLPR 调节肠道微生物群通过 PPARγ 信号通路缓解 ALD 脂肪变性。
