Is MASLD lost in translation in mice?

Area of Science:

• Hepatology
• Translational Medicine
• Preclinical Research

Background:

• Drug development for steatotic liver disease (SLD) faces significant challenges.
• Preclinical models are crucial for understanding disease mechanisms and testing therapeutics.
• Poor translation from animal models to human clinical outcomes is a persistent issue.

Purpose of the Study:

• To critically evaluate the utility of mouse models for studying human steatotic liver disease.
• To identify key variables that may explain the translational gap in SLD drug development.
• To highlight factors often overlooked in current preclinical research.

Main Methods:

• Review and discussion of existing literature on mouse models of steatotic liver disease.
• Analysis of factors influencing disease progression and phenotype in preclinical models.
• Comparison of experimental conditions in mouse models versus human SLD.

Main Results:

• Mouse models may not fully recapitulate the complexity of human steatotic liver disease.
• Aging and non-dietary hepatic stressors are significant confounding variables.
• These overlooked factors can lead to discrepancies between preclinical findings and human disease presentation.

Conclusions:

• Current mouse models require refinement to better reflect human steatotic liver disease.
• Incorporating variables like aging and diverse hepatic stressors is essential for improving translational success.
• Addressing these limitations can enhance the reliability of preclinical data for SLD drug development.