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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2016; 22(46): 10084-10092
Published online Dec 14, 2016. doi: 10.3748/wjg.v22.i46.10084
Sirtuins and nonalcoholic fatty liver disease
Fatiha Nassir, Jamal A Ibdah
Fatiha Nassir, Jamal A Ibdah, Research Service, Harry S Truman Memorial VA Hospital, University of Missouri, Columbia, MO 65201, United States
Fatiha Nassir, Jamal A Ibdah, Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
Author contributions: Nassir F reviewed the literature and wrote the manuscript; Ibdah JA edited the manuscript and approved the final version.
Conflict-of-interest statement: Authors declare no conflict of interests for this manuscript.
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: Jamal A Ibdah, MD, PhD, Professor, Director, Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, 1 Hospital Drive, DC043.00, CE405, Columbia, MO 65212, United States. ibdahj@health.missouri.edu
Telephone: +1-573-8827349 Fax: +1-573-8844595
Received: August 16, 2016
Peer-review started: August 17, 2016
First decision: September 20, 2016
Revised: October 12, 2016
Accepted: November 15, 2016
Article in press: November 16, 2016
Published online: December 14, 2016
Abstract

Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class III histone/protein deacetylases. Sirtuins (SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function. Sirtuins have been shown to play a key role in the development and rescue of various metabolic diseases including non-alcoholic fatty liver disease (NAFLD). NAFLD is currently the most chronic liver disease due mainly to high-calorie consumption and lower physical activity. No pharmacological approach is available to treat NAFLD, the current recommended treatment are lifestyle modification such as weight loss through calorie restriction and exercise. Recent studies have shown downregulation of sirtuins in human as well as animal models of NAFLD indicating an important role of sirtuins in the dynamic pathophysiology of NAFLD. In this review, we highlight the recent knowledge on sirtuins, their role in NAFLD and their unique potential role as novel therapeutic target for NAFLD treatment.

Keywords: SIRT1, SIRT3, Sirtuins, Non-alcoholic fatty liver disease

Core tip: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease with no effective pharmacological therapy. The discovery of treatment is hindered by the insufficient understanding of the pathophysiology of the disease. Sirtuins are key players in hepatic carbohydrate and lipid metabolism, insulin signaling, and inflammation and hence may represent a novel therapeutic target for NAFLD. However, the particular role for each sirtuin, the cross talk between sirtuins in different cell compartments or within a given organelle, and the development of selective sirtuins activators/inhibitors still need further investigation.