College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China; Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, 400016, China.
College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China; Chongqing Academy of Chinese Materia Medica, Chongqing, 400065, China.
Exp Cell Res. 2023 Sep 1;430(1):113721. doi: 10.1016/j.yexcr.2023.113721. Epub 2023 Jul 10.
The hepatitis B Virus X (HBx) protein plays a crucial role in the HBV-induced hepatic steatosis. Fatty acid transport protein 2 (FATP2) is a key protein that is involved in hepatic lipogenesis, and it was found to be highly expressed in various metabolic diseases. However, Whether FATP2 is a key factor in the pathogenesis of HBx-induced hepatic steatosis remains unclear. In this study, we found that FATP2 was up-regulated by HBx in vitro and in vivo and participated in HBx-induced hepatic lipid accumulation. Treatment of HBx-expressing cell lines and mice with FATP2 inhibitor (FATP2i) lipofermata ameliorated HBx-induced lipid accumulation and reduced oxidative stress and inflammation caused by lipid accumulation. Moreover, the liver injury of mouse was restored after FATP2i treatment. In summary, our results reveal that FATP2 is a key driver factor for HBx-induced hepatic lipid accumulation, and inhibition of FATP2 can ameliorates lipid accumulation caused by HBx. This study provides new insights into the mechanism of HBV-induced hepatic steatosis.
乙型肝炎病毒 X (HBx) 蛋白在 HBV 诱导的肝脂肪变性中起着关键作用。脂肪酸转运蛋白 2 (FATP2) 是一种参与肝内脂质生成的关键蛋白，它在各种代谢疾病中表达水平很高。然而，FATP2 是否是 HBx 诱导的肝脂肪变性发病机制中的关键因素尚不清楚。在这项研究中，我们发现 FATP2 被 HBx 在体外和体内上调，并参与 HBx 诱导的肝脂质堆积。用 FATP2 抑制剂 (FATP2i) lipofermata 处理表达 HBx 的细胞系和小鼠可改善 HBx 诱导的脂质堆积，并减轻脂质堆积引起的氧化应激和炎症。此外，FATP2i 处理后恢复了小鼠的肝损伤。总之，我们的结果表明 FATP2 是 HBx 诱导的肝脂质堆积的关键驱动因素，抑制 FATP2 可以改善 HBx 引起的脂质堆积。本研究为乙型肝炎病毒诱导的肝脂肪变性的机制提供了新的见解。
