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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2021; 27(1): 1-18
Published online Jan 7, 2021. doi: 10.3748/wjg.v27.i1.1
Experimental models of metabolic and alcoholic fatty liver disease
Delfin Gerard Buyco, Jasmin Martin, Sookyoung Jeon, Royce Hooks, Chelsea Lin, Rotonya Carr
Delfin Gerard Buyco, Jasmin Martin, Sookyoung Jeon, Royce Hooks, Chelsea Lin, Rotonya Carr, Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
Author contributions: Buyco DG wrote the first draft of the paper; Buyco DG, Martin J, Jeon S, Hooks R, Lin C and Carr RM performed the research for the manuscript and edited all drafts of the paper.
Conflict-of-interest statement: The authors report no conflicts of interest.
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: Rotonya Carr, MD, Assistant Professor, Division of Gastroenterology, University of Pennsylvania, 421 Curie Boulevard 907 Biomedical Research Center, Philadelphia, PA 19104, United States. rotonya.carr@pennmedicine.upenn.edu
Received: September 3, 2020
Peer-review started: September 3, 2020
First decision: October 17, 2020
Revised: November 1, 2020
Accepted: December 6, 2020
Article in press: December 6, 2020
Published online: January 7, 2021
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome (MetS). Because alcohol consumption in NAFLD patients is common, there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease (ALD). Indeed, MetS also significantly contributes to liver injury in ALD patients. This “syndrome of metabolic and alcoholic steatohepatitis” (SMASH) is thus expected to be a more prevalent presentation in liver patients, as the obesity epidemic continues. Several pre-clinical experimental models that couple alcohol consumption with NAFLD-inducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH. These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation, oxidative stress, and the induction of innate immune response. There are significant limitations in the applicability of these models to human disease, such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption. Thus, there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.

Keywords: Non-alcoholic fatty liver disease, Alcoholic liver disease, Non-alcoholic steatohepatitis, Animal models, Insulin resistance, Oxidative stress

Core Tip: Experimental animal and cell culture models have been developed to study the “syndrome of metabolic and alcoholic steatohepatitis” (SMASH), in which concomitant non-alcoholic fatty liver disease and alcoholic liver disease risk factors play a role in liver injury. These models demonstrate that obesity, metabolic syndrome, and alcohol consumption synergistically contribute to lipid dysregulation, oxidative stress, inflammation, and fibrogenesis. The pathogenesis of SMASH in these experimental models is dependent on obesogenic diet composition, alcohol consumption patterns, alcohol dosage, and genetic background.