Liu Peng, Li Heng, Xu Hongyu, Gong Jinsong, Jiang Min, Xu Zhenghong, Shi Jinsong
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China.
Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, 1000 Jinqi Road, Shanghai 201403, China.
iScience. 2023 Aug 29;26(10):107754. doi: 10.1016/j.isci.2023.107754. eCollection 2023 Oct 20.
Hepatic fibrosis is a classic pathological manifestation of metabolic chronic hepatopathy. The pathological process might either gradually deteriorate into cirrhosis and ultimately liver cancer with inappropriate nutrition supply, or be slowed down by several multifunctional nutrients, alternatively. Herein, we found diet with excessive phenylalanine (Phe) and tyrosine (Tyr) exacerbated hepatic fibrosis symptoms of liver dysfunction and gut microflora dysbiosis in mice. Chitooligosaccharides (COS) could ameliorate hepatic fibrosis with the regulation of amino acid metabolism by downregulating the mTORC1 pathway, especially that of Phe and Tyr, and also with the alleviation of the dysbiosis of gut microbiota, simultaneously. Conclusively, this work presents new insight into the role of Phe and Tyr in the pathologic process of hepatic fibrosis, while revealing the effectiveness and molecular mechanism of COS in improving hepatic fibrosis from the perspective of metabolites.
肝纤维化是代谢性慢性肝病的典型病理表现。该病理过程若营养供应不当可能会逐渐恶化为肝硬化并最终发展为肝癌,反之,几种多功能营养素则可能减缓这一过程。在此,我们发现富含过量苯丙氨酸(Phe)和酪氨酸(Tyr)的饮食会加剧小鼠肝功能障碍和肠道微生物群失调的肝纤维化症状。壳寡糖(COS)可通过下调mTORC1途径,特别是Phe和Tyr的途径来调节氨基酸代谢,同时缓解肠道微生物群的失调,从而改善肝纤维化。总之,这项工作揭示了Phe和Tyr在肝纤维化病理过程中的作用,同时从代谢物角度揭示了COS改善肝纤维化的有效性及分子机制。