Betulinic acid improves nonalcoholic fatty liver disease through YY1/FAS signaling pathway
Betulinic acid improves nonalcoholic fatty liver disease through YY1/FAS signaling pathway
复制标题
桦木酸通过 YY1/FAS 信号通路改善非酒精性脂肪肝
DOI：
10.1096/fj.202000546r
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发表时间：
2020-08-10
期刊：
影响因子：
4.8
通讯作者：
Zhang, Zhiguo
中科院分区：
文献类型：
--
作者：
Mu, Qian;Wang, Hui;Zhang, Zhiguo
世界范围内非酒精性脂肪性肝病（NAFLD）的患病率不断上升，表明迫切需要开发新的有效治疗策略。白桦酸（BA）是一种天然存在的植物衍生的五环三萜，具有显著的促进新陈代谢的作用。然而，BA在NAFLD中的药理作用和机制尚不清楚。在这里，我们表明，与小鼠相比，ba处理的高脂肪饮食小鼠和蛋氨酸-胆碱缺乏饮食小鼠对肝脏脂肪变性具有抗性。BA减轻脂肪酸合成、纤维化和炎症，并促进脂肪酸氧化。同时，BA处理显著抑制了体外和体内脂肪酸合成酶（FAS）的表达和活性。此外，BA通过抑制阴阳1 （YY1）转录抑制FAS表达，延缓肝细胞甘油三酯积累。总的来说，BA通过YY1/FAS途径保护肝细胞免受NAFLD异常脂质沉积的影响。我们的研究结果确立了BA在逆转NAFLD的可能治疗策略中的新作用。
The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide indicates the urgent need to develop novel and effective treatment strategies. Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has an outstanding effect in improving metabolism. However, the pharmacological action and mechanism of BA in NAFLD remain unclear. Here, we show that BA-treated high-fat diet mice and methionine-choline deficient diet-fed mice are resistant to hepatic steatosis when compared with vehicle-treated mice. BA alleviates fatty acid synthesis, fibrosis, and inflammation and promotes fatty acid oxidation. Meanwhile, fatty acid synthase (FAS) expression and activity are markedly inhibited with BA treatment both in vitro and in vivo. Moreover, BA inhibits FAS expression through transcriptional suppression of Yin Yang 1 (YY1), leading to retard hepatocytes triglyceride accumulation. Collectively, BA protects hepatocytes from abnormal lipid deposition in NAFLD through YY1/FAS pathway. Our findings establish a novel role of BA in representing a possible therapeutic strategy to reverse NAFLD.