Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis.
Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis.
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肠道 Akkermansia muciniphila 通过肠肝轴调节 L-天冬氨酸代谢，改善代谢功能障碍相关的脂肪肝
DOI：
10.1080/19490976.2021.1927633
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发表时间：
2021-01
期刊：
影响因子：
12.2
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Rao Y;Kuang Z;Li C;Guo S;Xu Y;Zhao D;Hu Y;Song B;Jiang Z;Ge Z;Liu X;Li C;Chen S;Ye J;Huang Z;Lu Y
肠道细菌嗜粘蛋白阿克曼氏菌（Akkermansia muciniphila）因其在治疗代谢紊乱（包括肥胖、糖尿病和代谢功能障碍相关脂肪肝（MAFLD））中的治疗潜力而日益被认识。然而，它的潜在机制涉及其众所周知的代谢作用需要进一步评估。本研究探讨了黄芪的治疗作用及其机制。通过使用高脂肪和高胆固醇（HFC）饮食诱导的肥胖小鼠模型，在干预MAFLD中使用嗜粘蛋白菌。A.嗜粘蛋白菌有效地逆转了肝脏中的MAFLD，如肝脂肪变性、炎症和肝损伤。这些治疗效果在长期停药后仍然存在，并且在接受抗肿瘤药物治疗的肥胖小鼠中略有减弱。A.嗜粘蛋白处理有效地增加了肠-肝轴中的线粒体氧化和胆汁酸代谢，改善了肠中氧化应激诱导的细胞凋亡，导致肠微生物群组成的重塑。这些代谢改善发生在肝脏中从肠道转运的L-天冬氨酸水平增加的情况下。L-天冬氨酸在体外或小鼠中的给药显示出类似的上述有益代谢作用，并有效地改善了MAFLD。总之，这些数据表明A. muciniphila与脂质氧化相关，并通过调节L-天冬氨酸代谢改善肠-肝相互作用。A.因此，嗜粘蛋白可能是临床干预MAFLD的潜在药物。
The gut bacterium Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-associated fatty liver disease (MAFLD). However, its underlying mechanism involved in its well-known metabolic actions needs further evaluation. The present study explored the therapeutic effect and mechanism of A. muciniphila in intervening MAFLD by using a high-fat and high-cholesterol (HFC) diet induced obese mice model. Mice treated with A. muciniphila efficiently reversed MAFLD in the liver, such as hepatic steatosis, inflammatory, and liver injury. These therapeutic effects persisted after long-term drug withdrawal and were slightly weakened in the antibiotics-treated obese mice. A. muciniphila treatment efficiently increased mitochondrial oxidation and bile acid metabolism in the gut-liver axis, ameliorated oxidative stress-induced cell apoptosis in gut, leading to the reshaping of the gut microbiota composition. These metabolic improvements occurred with increased L-aspartate levels in the liver that transported from the gut. The administration of L-aspartate in vitro or in mice displayed the similar beneficial metabolic effects mentioned above and efficiently ameliorated MAFLD. Together, these data indicate that the anti-MAFLD activity of A. muciniphila correlated with lipid oxidation and improved gut–liver interactions through regulating the metabolism of L-aspartate. A. muciniphila could be a potential agent for clinical intervention in MAFLD.
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