Cai Hong, Yang Chun-Hui, Gao Peng
Department of Clinical Laboratory, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China.
World J Gastroenterol. 2025 Apr 21;31(15):104528. doi: 10.3748/wjg.v31.i15.104528.
This article discusses a recent study by Wang that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease (MAFLD) to hepatocellular carcinoma (HCC). The study highlights the role of mitochondrial carnitine palmitoyltransferase II (CPT II) inactivity, which activates liver cancer stem cells marked by cluster of differentiation 44 (CD44) and CD24 expression, promoting HCC development. Using dynamic mouse models and clinical samples, Wang identified CPT II downregulation, mitochondrial membrane potential alterations, and reduced intrahepatic CD4 T cell as key drivers of disease progression. The findings link these changes to steroid biosynthesis and p53 signaling, contributing to T-cell dysfunction and immunosuppression. This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT II activity, mitochondrial function, and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.
本文讨论了王最近的一项研究，该研究揭示了驱动代谢功能障碍相关脂肪性肝病（MAFLD）进展为肝细胞癌（HCC）的代谢和免疫机制。该研究强调了线粒体肉碱棕榈酰转移酶II（CPT II）失活的作用，其激活了以分化簇44（CD44）和CD24表达为特征的肝癌干细胞，促进了HCC的发展。通过动态小鼠模型和临床样本，王确定CPT II下调、线粒体膜电位改变和肝内CD4 T细胞减少是疾病进展的关键驱动因素。这些发现将这些变化与类固醇生物合成和p53信号传导联系起来，导致T细胞功能障碍和免疫抑制。本文强调了这些结果在理解MAFLD发病机制方面的相关性，并讨论了针对CPT II活性、线粒体功能和免疫监视的潜在治疗策略，以预防或减轻晚期MAFLD中HCC的发展。
