Cai H, Yang CH, Gao P. Rethinking carnitine palmitoyltransferase II and liver stem cells in metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma. World J Gastroenterol 2025; 31(15): 104528 [PMID: 40309230 DOI: 10.3748/wjg.v31.i15.104528]
Corresponding Author of This Article
Peng Gao, PhD, Professor, Department of Clinical Laboratory, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian 116023, Liaoning Province, China. gaop@dmu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Apr 21, 2025; 31(15): 104528 Published online Apr 21, 2025. doi: 10.3748/wjg.v31.i15.104528
Rethinking carnitine palmitoyltransferase II and liver stem cells in metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma
Hong Cai, Chun-Hui Yang, Peng Gao
Hong Cai, Chun-Hui Yang, Peng Gao, Department of Clinical Laboratory, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Co-first authors: Hong Cai and Chun-Hui Yang.
Author contributions: Cai H and Yang CH contributed equally as co-first authors; Cai H contributed to the discussion, writing, and editing of the manuscript, as well as the review of the literature; Yang CH designed the overall concept and outline of the manuscript; Gao P reviewed and revised the manuscript for important intellectual content; All authors read and approved the final version of the manuscript to be published.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Peng Gao, PhD, Professor, Department of Clinical Laboratory, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian 116023, Liaoning Province, China. gaop@dmu.edu.cn
Received: December 28, 2024 Revised: February 27, 2025 Accepted: March 13, 2025 Published online: April 21, 2025 Processing time: 113 Days and 5.1 Hours
Abstract
This article discusses a recent study by Wang et al 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 et al 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.
Core Tip: This article reviews a recent study by Wang et al investigating how carnitine palmitoyltransferase II (CPT II) inactivity drives malignant progression in metabolic dysfunction-associated fatty liver disease (MAFLD) through aberrant lipid metabolism, T-cell dysfunction, and liver cancer stem cell activation. Their work revealed that mitochondrial damage and reduced CPT II activity under lipid-rich conditions may be early indicators of liver cancer risk, influencing immune cell profiles and the stem cell-like properties of hepatocytes. Understanding these processes could pave the way for novel preventative and therapeutic interventions targeting the metabolic and immunological underpinnings of MAFLD-related hepatocarcinogenesis.
