Sun Ye, Chen Qingling, Liu Yuxiao, Jiao Mengfan, Dai Zixing, Hou Xiaoxue, Liu Rui, Li Yuwen, Zhu Chuanlong
Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Infectious and Tropical Diseases, The Second Affiliated Hospital, NHC Key Laboratory of Tropical Disease Control, Hainan Medical University, Haikou, China.
J Infect Dis. 2025 Jan 8. doi: 10.1093/infdis/jiaf014.
The incidence of metabolic-associated steatotic liver disease in patients with chronic hepatitis B is increasing annually; however, the interaction between hepatitis B virus (HBV) infection and lipid metabolism remains unclear. This study attempted to clarify whether fatty acid metabolism regulation could alleviate mitochondrial dysfunction caused by HBV infection.
Public gene set of human livers was analyzed, and a proteomic analysis on mouse livers was conducted to explore metabolic disorders and affected organelles associated with HBV infection. The effect of decanoylcarnitine on fatty acid β-oxidation and mitochondria was investigated in vivo and in vitro. The pathways involved were shown by proteomic analysis and confirmed by Western blot.
HBV infection could cause fatty acid β-oxidation disorder and mitochondrial dysfunction in vivo and in vitro. CPT1A overexpression could improve mitochondrial function in hepatocytes. Furthermore, decanoylcarnitine supplementation could activate CPT1A expression, thus improving fatty acid metabolism and repairing mitochondrial dysfunction. Proteomic analysis of mouse livers suggests that decanoylcarnitine stimulates the peroxisome proliferator-activated receptor (PPAR) signaling pathway, and the PPARα was the most important among PPARs.
Impaired fatty acid metabolism and mitochondrial dysfunction in hepatocytes caused by HBV infection could be partially restored by exogenous supplementation of decanoylcarnitine. It elucidated the therapeutic potential of decanoylcarnitine in HBV infection and provided a new approach for diseases related to mitochondrial dysfunction.
慢性乙型肝炎患者中代谢相关脂肪性肝病的发病率逐年上升；然而，乙型肝炎病毒（HBV）感染与脂质代谢之间的相互作用仍不清楚。本研究试图阐明脂肪酸代谢调节是否可以减轻HBV感染引起的线粒体功能障碍。
分析人类肝脏的公共基因集，并对小鼠肝脏进行蛋白质组学分析，以探索与HBV感染相关的代谢紊乱和受影响的细胞器。在体内和体外研究癸酰肉碱对脂肪酸β-氧化和线粒体的影响。蛋白质组学分析显示相关途径，并通过蛋白质免疫印迹法进行确认。
HBV感染在体内和体外均可导致脂肪酸β-氧化紊乱和线粒体功能障碍。CPT1A过表达可改善肝细胞中的线粒体功能。此外，补充癸酰肉碱可激活CPT1A表达，从而改善脂肪酸代谢并修复线粒体功能障碍。对小鼠肝脏的蛋白质组学分析表明，癸酰肉碱刺激过氧化物酶体增殖物激活受体（PPAR）信号通路，且PPARα在PPARs中最为重要。
外源性补充癸酰肉碱可部分恢复HBV感染引起的肝细胞脂肪酸代谢受损和线粒体功能障碍。它阐明了癸酰肉碱在HBV感染中的治疗潜力，并为与线粒体功能障碍相关的疾病提供了一种新方法。
