Related Experiment Video
Updated: Feb 17, 2026
Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss
Published on: July 19, 2024
Non-alcoholic fatty liver disease (NAFLD) models in drug discovery
Banumathi K Cole1, Ryan E Feaver1, Brian R Wamhoff1
1a HemoShear Therapeutics , Charlottesville , VA USA.
Introduction:
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.
Insights
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) lack approved treatments, necessitating better preclinical models. This review examines animal and human organotypic models for studying NAFLD and evaluating new therapies.
Area of Science:
- Hepatology
- Translational Medicine
- Preclinical Research
Background:
- Non-alcoholic fatty liver disease (NAFLD), encompassing non-alcoholic steatohepatitis (NASH), represents a growing global health concern with no current approved treatments.
- The wide range of therapies in development indicates a lack of consensus on optimal therapeutic targets.
- There is a critical need for improved, translatable preclinical models to study progressive NAFLD and assess novel therapeutic strategies.
Purpose of the Study:
- To review existing mouse models of NASH used in preclinical studies.
- To examine complex organotypic in vitro and ex vivo liver models currently under development.
- To discuss the translational challenges and validation studies for these models in NAFLD research.
Main Methods:
- Literature review of published studies on mouse models of NASH.
- Analysis of organotypic in vitro and ex vivo liver models for NAFLD research.
- Evaluation of translational aspects and validation of preclinical models.
Main Results:
- Animal models provide whole-body context for drug effects but have species-specific limitations.
- Human organotypic models offer greater physiological relevance and translatability.
- Tiered approaches combining simpler screens with advanced models are recommended.
Conclusions:
- Effective preclinical models are crucial for advancing NAFLD and NASH research and drug development.
- Integrating advanced technologies like omics and biomarkers will enhance model utility.
- A combination of animal and human-based models, used strategically, is essential for understanding disease progression and evaluating therapeutics.
