Dysfunction in lipid metabolism may result in a decrease in hepatic autophagy, which contributes to the pathogenesis of non-alcoholic steatohepatitis. ATP-binding cassette transporter A1 transports free cholesterol and phospholipids to apolipoprotein A-I (apoA-I) to form nascent high-density lipoprotein particles. Results from previous studies showed that the overexpression of apoA-I significantly reduced levels of hepatic lipids and endoplasmic reticulum stress by modifying lipid transport. Here, we investigated the effects of apoA-I overexpression on hepatic autophagy in cultured hepatocytes and mice. The overexpression of apoA-I in HepG2 cells resulted in an increase in the levels of autophagy as well as the phosphorylation of AMP-activated protein kinase α (AMPKα) and ULK1 and a decrease in the phosphorylation of mammalian target of rapamycin (mTOR). An AMPK inhibitor and siRNA eliminated this apoA-I effect. Consistently, apoA-I transgenic mice showed increased autophagy and AMPKα phosphorylation. These results suggest that apoA-I overexpression alleviates steatohepatitis by increasing hepatic autophagy through the AMPK-mTOR-ULK1 pathway.

中文翻译：

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载脂蛋白AI通过AMPK途径改善肝脏自噬。

脂质代谢功能异常可能会导致肝脏自噬减少，这有助于非酒精性脂肪性肝炎的发病。ATP结合盒转运蛋白A1将游离胆固醇和磷脂转运至载脂蛋白AI（apoA-I），形成新生的高密度脂蛋白颗粒。先前研究的结果表明，通过修饰脂质转运，apoA-I的过表达显着降低了肝脂质和内质网应激水平。在这里，我们调查了apoA-I过表达对培养的肝细胞和小鼠肝脏自噬的影响。HepG2细胞中apoA-I的过表达导致自噬水平增加以及AMP激活的蛋白激酶α（AMPKα）和ULK1的磷酸化以及哺乳动物雷帕霉素靶标（mTOR）的磷酸化降低。AMPK抑制剂和siRNA消除了这种apoA-I效应。一致地，apoA-I转基因小鼠表现出增加的自噬和AMPKα磷酸化。这些结果表明，apoA-I的过表达通过增加通过AMPK-mTOR-ULK1途径的肝自噬减轻了脂肪性肝炎。