Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
Nutrients. 2023 Jan 22;15(3):586. doi: 10.3390/nu15030586.
The gut-liver axis plays a key role in the development and progression of non-alcoholic fatty liver disease (NAFLD). Due to the complexity and incomplete understanding of the cross-talk between the gut and liver, effective therapeutic targets are largely unknown. Free fatty acid receptors (FFARs) may bridge the cross-talk between the gut and liver. FFAR4 has received considerable attention due to its important role in lipid metabolism. However, the role of FFAR4 in this cross talk in NAFLD remains unclear. In this study, mice with high endogenous -3 PUFAs but FFAR4 deficiency were generated by crossbreeding Fat-1 and FFAR4 knockout mice. FFAR4 deficiency blocked the protective effects of high endogenous -3 PUFAs on intestinal barrier dysfunction and hepatic steatosis. In addition, FFAR4 deficiency decreased gut microbiota diversity and enriched , , and , and reduced , , , , , , and . Notably, FFAR4 deficiency co-regulated pantothenic acid and CoA biosynthesis, β-alanine metabolism, and sphingolipid metabolism pathways in the gut and liver, potentially associated with the aggravation of NAFLD. Together, the beneficial effects of -3 PUFAs on the gut and liver were mediated by FFAR4, providing insights on the role of FFAR4 in the treatment of NAFLD through the gut-liver axis.
肠-肝轴在非酒精性脂肪性肝病（NAFLD）的发生和进展中起着关键作用。由于对肠道和肝脏之间的相互作用的复杂性和不完全了解，有效的治疗靶点在很大程度上尚不清楚。游离脂肪酸受体（FFARs）可能架起了肠道和肝脏之间的交流桥梁。FFAR4 因其在脂质代谢中的重要作用而受到广泛关注。然而，FFAR4 在 NAFLD 中这种相互作用中的作用尚不清楚。在这项研究中，通过杂交 Fat-1 和 FFAR4 敲除小鼠，生成了内源性高 -3PUFAs 但缺乏 FFAR4 的小鼠。FFAR4 缺乏阻断了内源性高 -3PUFAs 对肠道屏障功能障碍和肝脂肪变性的保护作用。此外，FFAR4 缺乏降低了肠道微生物群落的多样性，并丰富了、、和，减少了、、、、、、和。值得注意的是，FFAR4 缺乏共同调节了肠道和肝脏中的泛酸和 CoA 生物合成、β-丙氨酸代谢和鞘脂代谢途径，这可能与 NAFLD 的加重有关。总之，-3PUFAs 通过 FFAR4 对肠道和肝脏发挥有益作用，为通过肠-肝轴治疗 NAFLD 中 FFAR4 的作用提供了新的见解。
Zotero 插件
