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World J Hepatol. Feb 27, 2015; 7(2): 226-234
Published online Feb 27, 2015. doi: 10.4254/wjh.v7.i2.226
Micro RNAs in the development of non-alcoholic fatty liver disease
Glenn S Gerhard, Johanna K DiStefano
Glenn S Gerhard, Department of Medical Genetics and Molecular Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, United States
Johanna K DiStefano, Diabetes, Cardiovascular and Metabolic Diseases Division, Translational Genomics Research Institute, Phoenix, AZ 85004, United States
Author contributions: Gerhard GS and Distefano JK contributed to this paper.
Supported by The National Institutes of Health DK091601 (JKD and GSG), P30 DK072488 (GSG and CDS); and the Translational Genomics Research Institute.
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: Johanna K DiStefano, PhD, Diabetes, Cardiovascular and Metabolic Diseases Division, Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, AZ 85004, United States. jdistefano@tgen.org
Telephone: +1-602-3438812 Fax: +1-602-3438844
Received: August 16, 2014
Peer-review started: August 17, 2014
First decision: September 28, 2014
Revised: October 28, 2014
Accepted: November 17, 2014
Article in press: November 19, 2014
Published online: February 27, 2015
Processing time: 181 Days and 8.5 Hours
Abstract

Nonalcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD) refers to a group of disorders that arise from the accrual of fat in hepatocytes. Although various factors have been associated with the development of NAFLD, including genetic predisposition and environmental exposures, little is known about the underlying pathogenesis of the disease. Research efforts are ongoing to identify biological targets and signaling pathways that mediate NAFLD. Emerging evidence has implicated a role for micro RNAs (miRNAs), short single-stranded molecules that regulate gene expression either transcriptionally, through targeting of promoter regions, or post-transcriptionally, by blocking translation or promoting cleavage of specific target mRNAs. Several miRNAs have been associated with NAFLD, although our understanding of the biology underlying their role is still emerging. The goal of this review is to present an overview of the current state of knowledge of miRNAs involved in the development of NAFLD across a range of in vitro and in vivo models, including miRNAs that contribute to pathological mechanisms related to fatty liver in humans. Much less is known about the specific targets of miRNAs in cells, nor the molecular mechanisms involved in the development and progression NAFLD and related outcomes. More recently, the identification and validation of miRNA signatures in serum may facilitate the development of improved methods for diagnosis and clinical monitoring of disease progression.

Keywords: MiRNA; Nonalcoholic fatty liver disease; Cell culture; Mouse; Human

Core tip: Available data on miRNAs in nonalcoholic fatty liver disease (NAFLD) are largely derived from various cell culture and animal models. Reflecting an emerging field, little cross-model concordance is present and few human data are available for comparison with cell culture and animal model results. Although the generation of human data may be limited by the availability of tissue samples, recent reports of circulating miRNAs from NAFLD patients hold promise for significant progress for diagnosis and clinical monitoring of disease progression.