Review
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2023; 29(12): 1765-1778
Published online Mar 28, 2023. doi: 10.3748/wjg.v29.i12.1765
Mitochondrial carnitine palmitoyltransferase-II dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis
Min Yao, Ping Zhou, Yan-Yan Qin, Li Wang, Deng-Fu Yao
Min Yao, Department of Medical Immunology, Medical School of Nantong University & Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Ping Zhou, Yan-Yan Qin, Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
Li Wang, Research Center for Intelligent Information Technology, Nantong University, Nantong 226019, Jiangsu Province, China
Deng-Fu Yao, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Author contributions: Yao M, Zhou P and Qin YY contributed equally to this work, designed, collected and analyzed the data, prepared the first draft and performed subsequent revisions; Yao DF and Wang L provided critical review; All authors have read and agreed to the published version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81873915 and No. 31872738; the Key Plan of Nantong S&T Development, No. MS12020021; and the S&T Program of Medical School of Nantong University, No. TDYX2021010.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Deng-Fu Yao, MD, PhD, Full Professor, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, No. 20 West Temple Road, Nantong 226001, Jiangsu Province, China. yaodf@ahnmc.com
Received: June 20, 2022
Peer-review started: June 20, 2022
First decision: August 1, 2022
Revised: August 4, 2022
Accepted: March 9, 2023
Article in press: March 9, 2023
Published online: March 28, 2023
Processing time: 281 Days and 7.3 Hours
Abstract

Nonalcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world. The complex mechanisms of NAFLD formation are still under identification. Carnitine palmitoyltransferase-II (CPT-II) on inner mitochondrial membrane (IMM) regulates long chain fatty acid β-oxidation, and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD. The sequences of its peptide chain and DNA nucleotides have been identified, and the catalytic activity of CPT-II is affected on its gene mutations, deficiency, enzymatic thermal instability, circulating carnitine level and so on. Recently, the CPT-II dysfunction has been discovered in models of liver lipid accumulation. Meanwhile, the malignant transformation of hepatocyte-related CD44+ stem T cell activation, high levels of tumor-related biomarkers (AFP, GPC3) and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology. This review focuses on some of the progress of CPT-II inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.

Keywords: Carnitine palmitoyl transferase-II; Nonalcoholic fatty liver disease; Fatty acid β-oxidation; Carnitine; Hepatocyte malignant transformation; Mitochondrial membrane

Core Tip: The complex mechanisms of nonalcoholic fatty liver disease formation are still under identification. Hepatic carnitine palmitoyl transferase-II (CPT-II) on inner mitochondrial membrane regulates long chain fatty acid β-oxidation and this abnormality has had more attention paid to it by basic and clinical research. The sequences of its peptide chain and DNA nucleotides have been identified and the catalytic activity of CPT-II is affected on its gene mutations, deficiency, enzymatic thermal instability, circulating carnitine level and so on. CPT-II dysfunction has been discovered in models of lipid accumulation. Meanwhile, the malignant transformation of hepatocyte-related CD44+ stem T cell activation, high levels of tumor-related biomarkers and abnormal Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.