Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb;13(2):193-205.
doi: 10.1080/17460441.2018.1410135. Epub 2017 Dec 6.

Non-alcoholic fatty liver disease (NAFLD) models in drug discovery

Affiliations
Review

Non-alcoholic fatty liver disease (NAFLD) models in drug discovery

Banumathi K Cole et al. Expert Opin Drug Discov. 2018 Feb.

Abstract

The progressive disease spectrum of non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is a rapidly emerging public health crisis with no approved therapy. The diversity of various therapies under development highlights the lack of consensus around the most effective target, underscoring the need for better translatable preclinical models to study the complex progressive disease and effective therapies. Areas covered: This article reviews published literature of various mouse models of NASH used in preclinical studies, as well as complex organotypic in vitro and ex vivo liver models being developed. It discusses translational challenges associated with both kinds of models, and describes some of the studies that validate their application in NAFLD. Expert opinion: Animal models offer advantages of understanding drug distribution and effects in a whole body context, but are limited by important species differences. Human organotypic in vitro and ex vivo models with physiological relevance and translatability need to be used in a tiered manner with simpler screens. Leveraging newer technologies, like metabolomics, proteomics, and transcriptomics, and the future development of validated disease biomarkers will allow us to fully utilize the value of these models to understand disease and evaluate novel drugs in isolation or combination.

Keywords: Non-alcoholic fatty liver disease (NAFLD); fibrosis; hepatic stellate cell; hepatocyte; inflammation; non-alcoholic steatohepatitis (NASH); organotypic; preclinical; steatosis.

PubMed Disclaimer

Similar articles

Cited by

Publication types

LinkOut - more resources