Mitochondrial carnitine palmitoyltransferase-II dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis.

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.

• Authors: Min Yao, Ping Zhou, Yan-Yan Qin, Li Wang, Deng-Fu Yao
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 29 Issue 12 Pg. 1765-1778 (Mar 28 2023) ISSN: 2219-2840 [Electronic] United States
• PMID: 37032731 (Publication Type: Journal Article, Review)
• Copyright: ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

Chemical References

• Carnitine O-Palmitoyltransferase
• Fatty Acids
• Carnitine
• GPC3 protein, human
• Glypicans

Topics

• Humans
• Non-alcoholic Fatty Liver Disease (metabolism)
• Carnitine O-Palmitoyltransferase (genetics, metabolism)
• Liver (metabolism)
• Carcinogenesis (metabolism)
• Fatty Acids (metabolism)
• Oxidation-Reduction
• Carnitine (metabolism)
• Glypicans (metabolism)