Micro RNAs in the development of non-alcoholic fatty liver disease

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.