Ghazali R, Mehta KJ, Bligh SA, Tewfik I, Clemens D, Patel VB. High omega arachidonic acid/docosahexaenoic acid ratio induces mitochondrial dysfunction and altered lipid metabolism in human hepatoma cells. World J Hepatol 2020; 12(3): 84-98 [PMID: 32231762 DOI: 10.4254/wjh.v12.i3.84]
Corresponding Author of This Article
Vinood B Patel, FRSC, PhD, Reader (Associate Professor), School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, United Kingdom. v.b.patel@westminster.ac.uk
Research Domain of This Article
Pathology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
Reem Ghazali, SW Annie Bligh, Ihab Tewfik, Vinood B Patel, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom
Reem Ghazali, Clinical Biochemistry Department, Faculty of medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Kosha J Mehta, Centre for Education, Faculty of Life Sciences and Medicine, King's College London SE1 1UL, United Kingdom
SW Annie Bligh, Caritas Institute of Higher Education, Hong Kong 999077, China
Dahn Clemens, Nebraska and Western Iowa Veterans Administration Medical Center and Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
Author contributions: Ghazali R was the primary researcher, collected and analyzed data; Mehta K wrote the manuscript, analyzed data, prepared figures and formatted manuscript for publication; Bligh A provided intellectual input and feedback on manuscript; Tewfik I provided intellectual input and feedback on manuscript; Clemens D provided intellectual input and feedback on manuscript; Patel V conceived, designed and directed the study, analyzed data and approved the article to be published.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: All authors have reviewed and approved the data.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Vinood B Patel, FRSC, PhD, Reader (Associate Professor), School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, United Kingdom. v.b.patel@westminster.ac.uk
Received: July 14, 2019 Peer-review started: July 16, 2019 First decision: November 2, 2019 Revised: December 24, 2019 Accepted: January 14, 2020 Article in press: January 14, 2020 Published online: March 27, 2020 Processing time: 90 Days and 22 Hours
Core Tip
Core tip: A high ratio of omega 6:3 fatty acids in the diet has been implicated in the development of non-alcoholic fatty liver disease, a growing epidemic of major concern. The cellular pathology induced by such high ratios remains unknown. Here, we observed that in human hepatoma HepG2 (VL-17A) cells, high omega-6:omega-3 ratio reduced mitochondrial activity, increased triglyceride accumulation, elevated reactive oxygen species levels and interrupted several mitochondrial functions. Moreover, the increased expression of stearoyl-CoA desaturase, decreased expression of peroxisome proliferator-activated receptor alpha and elevation in cannabinoid receptor-1 expression collectively lead to lipogenesis and lipotoxicity, which are key features of non-alcoholic fatty liver disease development.
