Branched-chain amino acids alleviate NAFLD via inhibiting de novo lipogenesis and activating fatty acid β-oxidation in laying hens

文献类型： 外文期刊

第一作者： Jian, Huafeng

作者： Jian, Huafeng;Li, Ru;Huang, Xuan;Li, Jiankui;Li, Yan;Dong, Xinyang;Zou, Xiaoting;Zhu, Mingkun;Zhu, Mingkun;Jian, Huafeng;Ma, Jiangang;Yang, Hua

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关键词： Branched-chain amino acids; Nonalcoholic fatty liver disease; Tryptophan-ILA-AHR; MAPK9; Ubiquitination

期刊名称：REDOX BIOLOGY （ 影响因子：11.9； 五年影响因子：13.1 ）

ISSN： 2213-2317

年卷期： 2024 年 77 卷

页码：

收录情况： SCI

摘要： The adverse metabolic impacts of branched-chain amino acids (BCAA) have been elucidated are mediated by isoleucine and valine. Dietary restriction of isoleucine promotes metabolic health and increases lifespan. However, a high protein diet enriched in BCAA is presently the most useful therapeutic strategy for nonalcoholic fatty liver disease (NAFLD), yet, its underlying mechanism remains largely unknown. Fatty liver hemorrhagic syndrome (FLHS), a specialized laying hen NAFLD model, can spontaneously develop fatty liver and hepatic steatosis under a high-energy and high-protein dietary background that the pathogenesis of FLHS is similar to human NAFLD. The mechanism underlying dietary BCAA control of NAFLD development in laying hens remains unclear. Herein, we demonstrate that dietary supplementation with 67 % High BCAA has unique mitigative impacts on NAFLD in laying hens. A High BCAA diet alleviates NAFLD, by inhibiting the tryptophan-ILA-AHR axis and MAPK9-mediated de novo lipogenesis (DNL), promoting ketogenesis and energy metabolism, and activating PPAR-RXR and pexophagy to promote fatty acid beta-oxidation. Furthermore, we uncover that High BCAA strongly activates ubiquitin-proteasome autophagy via downregulating UFMylation to trigger MAPK9-mediated DNL, fatty acid elongation and lipid droplet formation-related proteins ubiquitination degradation, activating PPARRXR and pexophagy mediated fatty acid beta-oxidation and lipolysis. Together, our data highlight moderating intake of high BCAA by inhibiting the AHR/MAPK9 are promising new strategies in NAFLD and FLHS treatment.

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