Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2024; 30(47): 5055-5069
Published online Dec 21, 2024. doi: 10.3748/wjg.v30.i47.5055
Carnitine palmitoyltransferase-II inactivity promotes malignant progression of metabolic dysfunction-associated fatty liver disease via liver cancer stem cell activation
Ling-Ling Wang, Yu-Ming Lu, Yi-Han Wang, Yi-Fan Wang, Rong-Fei Fang, Wen-Li Sai, Deng-Fu Yao, Min Yao
Ling-Ling Wang, Yu-Ming Lu, Yi-Han Wang, Yi-Fan Wang, Min Yao, Department of Immunology, Medical School, Nantong University, Nantong 226001, Jiangsu Province, China
Rong-Fei Fang, Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Wen-Li Sai, Deng-Fu Yao, Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Co-first authors: Ling-Ling Wang and Yu-Ming Lu.
Co-corresponding authors: Deng-Fu Yao and Min Yao.
Author contributions: Wang LL, Lu YM, and Wang YH conceptualized and designed the research; Wang YH, Wang YF, and Fang RF screened patients and acquired clinical data; Yang YF and Sai WL collected blood specimens and performed laboratory analysis; Fang RF and Sai WL performed data analysis; Yao DF and Yao M acquired the funding and wrote the manuscript. All the authors have read and approved the final manuscript. Wang LL, Lu YM, and Wang YH were responsible for patient screening, enrollment, and collection of clinical data and blood samples. Both authors have made crucial and indispensable contributions toward the completion of the project and thus have qualified as the co-first authors of the paper. Both Yao M and Yao DF played important and indispensable roles in the experimental design, data interpretation, and manuscript preparation as co-corresponding authors. Yao M and Yao DF applied for and obtained the funds for this research project, as well as conceptualized, designed, and supervised the entire process of the project. Yao M and Yao DF searched the literature and revised and submitted the early version of the manuscript with a focus on the association between MAFLD and LCSCs, and they were instrumental and responsible for data reanalysis and reinterpretation, figure plotting, comprehensive literature search, preparation and submission of the current version of the manuscript, with a new focus on LCSCs as predictors of MAFLD and potential underlying mechanisms. This collaboration between Yao M and Yao DF is crucial for the publication of this manuscript and other manuscripts still in preparation.
Supported by the National Natural Science Foundation of China, No. 32470985 and No. 81673241.
Institutional review board statement: Patient recruitment was approved by the Ethics Committee of Nantong University (NTU-2021-43).
Institutional animal care and use committee statement: The study involving the rat model was approved by the guidelines of the Animal Care and Use Committee of Nantong University (S20200318-017).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Min Yao, MD, PhD, Postdoc, Professor, Department of Immunology, Medical School, Nantong University, No. 19 Qixiu Road, Nantong 226001, Jiangsu Province, China. erbei@ntu.edu.cn
Received: July 9, 2024
Revised: October 6, 2024
Accepted: November 5, 2024
Published online: December 21, 2024
Processing time: 140 Days and 5 Hours
Core Tip

Core Tip: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the main chronic liver diseases. The present study investigated the dynamic alterations in mitochondrial carnitine palmitoyl transferase-II (CPT-II) in T cells and liver cancer stem cell (LCSC) activation in MAFLD during hepatocyte malignant progression under lipid accumulation. There was a loss of mitochondrial CPT-II activity and a decrease in the mitochondrial membrane potential with decreasing numbers of CD3+ or CD4+ T cells. Mechanistically, CPT-II inactivity via the loss of innate immune function with abnormal activation of LCSCs promotes the malignant progression of MAFLD. These results suggest that CPT-II prevents lipid accumulation and LCSC activation, as well as improves IL-CD3/CD4 T cell function for hepatocellular carcinoma immunotherapy and delays MAFLD malignant progression.