Mitochondrial carnitine palmitoyl transferase-Ⅱ inactivity aggravates lipid accumulation in rat hepatocarcinogenesis

AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. Acc...

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Published in:World journal of gastroenterology : WJG 2017-01, Vol.23 (2), p.256-264
Main Authors: Gu, Juan-Juan, Yao, Min, Yang, Jie, Cai, Yin, Zheng, Wen-Jie, Wang, Li, Yao, Deng-Bing, Yao, Deng-Fu
Format: Article
Language:English
Subjects:
2-Acetylaminofluorene - toxicity
Alanine Transaminase - blood
Animals
Aspartate Aminotransferases - blood
Basic Study
Carcinogenesis - metabolism
Carcinoma, Hepatocellular - blood
Carcinoma, Hepatocellular - chemically induced
Carcinoma, Hepatocellular - metabolism
Carnitine O-Palmitoyltransferase - metabolism
Cholesterol - blood
Diet, High-Fat - adverse effects
Hepatocytes - metabolism
Immunohistochemistry
Lipid Metabolism
Liver - cytology
Liver Neoplasms, Experimental - blood
Liver Neoplasms, Experimental - chemically induced
Liver Neoplasms, Experimental - metabolism
Male
Mitochondria - enzymology
Non-alcoholic Fatty Liver Disease - blood
Non-alcoholic Fatty Liver Disease - etiology
Non-alcoholic Fatty Liver Disease - metabolism
Rats
Rats, Sprague-Dawley
Triglycerides - blood
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Summary:AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v23.i2.256