Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. May 15, 2016; 7(2): 211-217
Published online May 15, 2016. doi: 10.4291/wjgp.v7.i2.211
Insulin resistance in development and progression of nonalcoholic fatty liver disease
Shahinul Alam, Golam Mustafa, Mahabubul Alam, Nooruddin Ahmad
Shahinul Alam, Golam Mustafa, Mahabubul Alam, Nooruddin Ahmad, Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka 1000, Bangladesh
Author contributions: All authors contributed equally to this paper in the conception and design of the study, literature review and analysis, drafting, critical revisions and editing; all authors approved the final version of the manuscript.
Conflict-of-interest statement: The authors have no potential conflicts of interest.
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:
Correspondence to: Shahinul Alam, Associate Professor, Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka 1000, Bangladesh.
Telephone: +88-019-73007173
Received: August 31, 2015
Peer-review started: September 5, 2015
First decision: November 30, 2015
Revised: January 3, 2016
Accepted: March 7, 2016
Article in press: March 9, 2016
Published online: May 15, 2016

Although insulin resistance (IR) is strongly associated with nonalcoholic fatty liver disease (NAFLD), the association of IR and NAFLD is not universal and correlation between IR and severity of NAFLD is still controversial. In this review, we summarize recent evidence that partially dissociates insulin resistance from NAFLD. It has also been reported that single-nucleotide polymorphisms in the diacylglycerol acyltransferase gene, rather than IR, account for the variability in liver fat content. Polymorphisms of the patatin-like phospholipase 3 gene have also been reported to be associated with NAFLD without metabolic syndrome, which suggests that genetic conditions that promote the development of fatty changes in the liver may occur independently of IR. Moreover, environmental factors such as nutrition and physical activity as well as small intestinal bacterial overgrowth have been linked to the pathogenesis of NAFLD, although some of the data are conflicting. Therefore, findings from both genetically engineered animal models and humans with genetic conditions, as well as recent studies that have explored the role of environmental factors, have confirmed the view that NAFLD is a polygenic disease process caused by both genetic and environmental factors. Therefore, IR is not the sole predictor of the pathogenesis of NAFLD.

Keywords: Nonalcoholic fatty liver disease, Insulin resistance, Metabolic syndrome, Diabetes, Nonalcoholic steatohepatitis

Core tip: Insulin resistance is considered as the major contributor for the development and progression of nonalcoholic fatty liver disease (NAFLD). However, recent evidence that has shown that non-obese individuals from developing countries are also affected by NAFLD, thus the conventional paradigm of NAFLD as the “hepatic manifestation of metabolic syndrome” has become outdated. Recent studies have highlighted novel pathophysiological mechanisms for the development and progression of NAFLD. Insulin resistance contributes to the disease process, but it is evident that environmental and genetic factors also contribute for development of necroinflammation and subsequent progression to fibrosis. This review provides a summary of current knowledge of the pathogenesis of NAFLD and discusses factors that dissociate insulin resistance from NAFLD.