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Astragaloside I Promotes Lipophagy and Mitochondrial Biogenesis to Improve Hyperlipidemia by Regulating Akt/mTOR/TFEB Pathway
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-03 , DOI: 10.1021/acs.jafc.4c03172 Jie Zhao 1 , Gai Gao 1 , Jing Ding 1 , Wei Liu 2 , Tao Wang 1 , Liang Zhao 1 , Jiangyan Xu 1 , Zhenqiang Zhang 1 , Xiaowei Zhang 1 , Zhishen Xie 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-03 , DOI: 10.1021/acs.jafc.4c03172 Jie Zhao 1 , Gai Gao 1 , Jing Ding 1 , Wei Liu 2 , Tao Wang 1 , Liang Zhao 1 , Jiangyan Xu 1 , Zhenqiang Zhang 1 , Xiaowei Zhang 1 , Zhishen Xie 1
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The simultaneous enhancement of lipophagy and mitochondrial biogenesis has emerged as a promising strategy for lipid lowering. The transcription factor EB (TFEB) exhibits a dual role, whereby it facilitates the degradation of lipid droplets (LDs) through the process of lipophagy while simultaneously stimulating mitochondrial biogenesis to support the utilization of lipophagy products. The purpose of this study was to explore the effect of astragaloside I (AS I) on hyperlipidemia and elucidate its underlying mechanism. AS I improved serum total cholesterol and triglyceride levels and reduced hepatic steatosis and lipid accumulation in db/db mice. AS I enhanced the fluorescence colocalization of LDs and autophagosomes and promoted the proteins and genes related to the autolysosome. Moreover, AS I increased the expression of mitochondrial biogenesis-related proteins and genes, indicating that AS I promoted lipophagy and mitochondrial biogenesis. Mechanistically, AS I inhibits the protein level of p-TFEB (ser211) expression and promotes TFEB nuclear translocation. The activation of TFEB by AS I was impeded upon the introduction of the mammalian target of rapamycin (mTOR) agonist MHY1485. The inhibition of p-mTOR by AS I and the activation of TFEB were no longer observed after administration of the Akt agonist SC-79, which indicated that AS I activated TFEB to promote lipophagy-dependent on the Akt/mTOR pathway and may be a potentially effective pharmaceutical and food additive for the treatment of hyperlipidemia.
中文翻译：
黄芪甲苷 I 通过调节 Akt/mTOR/TFEB 通路促进脂肪吞噬和线粒体生物发生以改善高脂血症
脂肪吞噬和线粒体生物发生的同时增强已成为一种很有前途的降脂策略。转录因子 EB （TFEB） 具有双重作用，它通过脂肪吞噬过程促进脂滴 （LD） 的降解，同时刺激线粒体生物发生以支持脂肪吞噬产物的利用。本研究的目的是探讨黄芪甲苷 I （AS I） 对高脂血症的影响并阐明其潜在机制。AS I 改善了 db/db 小鼠的血清总胆固醇和甘油三酯水平，减少了肝脏脂肪变性和脂质积累。AS I 增强了 LDs 和自噬体的荧光共定位，并促进了与自噬溶酶体相关的蛋白质和基因。此外，AS I 增加了线粒体生物发生相关蛋白和基因的表达，表明 AS I 促进了脂肪吞噬和线粒体生物发生。从机制上讲，AS I 抑制 p-TFEB （ser211） 表达的蛋白水平并促进 TFEB 核转位。在引入哺乳动物雷帕霉素靶标 （mTOR） 激动剂 MHY1485后，AS I 对 TFEB 的激活受到阻碍。施用 Akt 激动剂 SC-79 后，不再观察到 AS I 对 p-mTOR 的抑制和 TFEB 的激活，这表明 AS I 激活 TFEB 以促进依赖于 Akt/mTOR 通路的脂肪吞噬，可能是治疗高脂血症的潜在有效药物和食品添加剂。
更新日期：2024-09-03
中文翻译：
黄芪甲苷 I 通过调节 Akt/mTOR/TFEB 通路促进脂肪吞噬和线粒体生物发生以改善高脂血症
脂肪吞噬和线粒体生物发生的同时增强已成为一种很有前途的降脂策略。转录因子 EB （TFEB） 具有双重作用，它通过脂肪吞噬过程促进脂滴 （LD） 的降解，同时刺激线粒体生物发生以支持脂肪吞噬产物的利用。本研究的目的是探讨黄芪甲苷 I （AS I） 对高脂血症的影响并阐明其潜在机制。AS I 改善了 db/db 小鼠的血清总胆固醇和甘油三酯水平，减少了肝脏脂肪变性和脂质积累。AS I 增强了 LDs 和自噬体的荧光共定位，并促进了与自噬溶酶体相关的蛋白质和基因。此外，AS I 增加了线粒体生物发生相关蛋白和基因的表达，表明 AS I 促进了脂肪吞噬和线粒体生物发生。从机制上讲，AS I 抑制 p-TFEB （ser211） 表达的蛋白水平并促进 TFEB 核转位。在引入哺乳动物雷帕霉素靶标 （mTOR） 激动剂 MHY1485后，AS I 对 TFEB 的激活受到阻碍。施用 Akt 激动剂 SC-79 后，不再观察到 AS I 对 p-mTOR 的抑制和 TFEB 的激活，这表明 AS I 激活 TFEB 以促进依赖于 Akt/mTOR 通路的脂肪吞噬，可能是治疗高脂血症的潜在有效药物和食品添加剂。
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