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.

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.