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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2017; 23(2): 256-264
Published online Jan 14, 2017. doi: 10.3748/wjg.v23.i2.256
Mitochondrial carnitine palmitoyl transferase-II inactivity aggravates lipid accumulation in rat hepatocarcinogenesis
Juan-Juan Gu, Min Yao, Jie Yang, Yin Cai, Wen-Jie Zheng, Li Wang, Deng-Bing Yao, Deng-Fu Yao
Juan-Juan Gu, Wen-Jie Zheng, Deng-Fu Yao, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Min Yao, Department of Immunology, Medical College of Nantong University, Nantong 226001, Jiangsu Province, China
Jie Yang, Pharmacy College of Nantong University, Nantong 226001, Jiangsu Province, China
Yin Cai, Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Li Wang, Department of Medical Informatics, Medical College of Nantong University, Nantong 226001, Jiangsu Province, China
Deng-Bing Yao, Department of Biochemistry, School of Life Science, Nantong University, Nantong 226001, Jiangsu Province, China
Author contributions: Gu JJ, Yao M and Zheng WJ contributed equally to this work; Gu JJ, Yao M and Wang L designed and performed the research; Yang J, Cai Y and Yao DB contributed new reagents/analytic tools; Yao M, Zheng WJ and Wang L analyzed the data; Gu JJ and Yao DF wrote the paper; Yao DF is the guarantor; All authors have read and approved the final version to be published.
Supported by the National Natural Science Foundation, No. 81673241, No. 81200634, No. 81370982; the program of Jiangsu Key Research Plan, No. BE2016698; and the International Science and Technology Cooperation Program of China, No. 2013DFA32150.
Institutional review board statement: The study was reviewed and approved by the Affiliated Hospital of Nantong University, China.
Institutional animal care and use committee statement: The study was reviewed and approved by Nantong University, China.
Conflict-of-interest statement: No potential conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Deng-Fu Yao, MD, PhD, Professor, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, No. 20 West Temple Road, Nantong 226001, Jiangsu Province, China.
yaodf@ahnmc.com
Telephone: +86-51385052297 Fax: +86-51385052523
Received: August 25, 2016
Peer-review started: August 28, 2016
First decision: September 21, 2016
Revised: September 29, 2016
Accepted: October 31, 2016
Article in press: October 31, 2016
Published online: January 14, 2017
Processing time: 139 Days and 23.2 Hours
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, precancerous, 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 amino-transferases [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.
Core tip: Nonalcoholic fatty liver disease (NAFLD) is one of the main risk factors for hepatocellular carcinoma, except for chronic infection with hepatitis B virus or hepatitis C virus as well as other non-viral liver diseases. However, the pathogenesis of NAFLD formation still need to be elucidated. We have successfully investigated the dynamic alteration of carnitine palmitoyl transferase II (CPT-II) expression located on the mitochondrial inner membrane during malignant transformation of rat hepatocytes under lipid accumulation and first discovered that the progressively decreasing of CPT-II expression in hepatocarcinogenesis might lead to abnormal hepatic lipid accumulation and promote the malignant transformation of hepatocytes.
