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Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss
Published on: July 19, 2024
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The LIDPAD Mouse Model Captures the Multisystem Interactions and Extrahepatic Complications in MASLD
Zun Siong Low1, Damien Chua1, Hong Sheng Cheng1
1Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, 11 Mandalay Road, Singapore, 308232, Singapore.
Summary
A new mouse model, LIDPAD, accurately mimics human metabolic dysfunction-associated steatotic liver disease (MASLD), showing gut-liver-pancreas axis involvement. This model
Area of Science:
- * Hepatology and metabolic disease research.
- * Development and validation of preclinical models for human diseases.
Background:
- * Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern.
- * Current MASLD management faces challenges, necessitating better preclinical models that reflect human disease complexity and comorbidities.
Purpose of the Study:
- * To introduce and characterize the Liver Disease Progression Aggravation Diet (LIDPAD) murine model for MASLD.
- * To assess the LIDPAD model's fidelity in recapitulating human MASLD phenotypes, genetics, and metabolic hallmarks.
- * To establish a computational pipeline for transcriptomic-guided disease staging and comparative analysis.
Main Methods:
- * Development of the LIDPAD diet-induced murine model under controlled conditions.
- * Comprehensive characterization of phenotypic, genetic, and metabolic features of the LIDPAD model.
- * Creation and validation of a computational pipeline for transcriptomic analysis and disease staging against human datasets.
- * Evaluation of the LIDPAD model's response to dietary interventions.
Main Results:
- * The LIDPAD model effectively replicates key MASLD features, including multiorgan communication and disease progression over 4-16 weeks.
- * Early gut-liver dysregulation and compensatory pancreatic islet hyperplasia were identified, highlighting the gut-pancreas axis.
- * The model demonstrated high similarity to human MASLD, confirmed by aligned molecular signatures and responsiveness to dietary changes.
- * Transcriptomic analysis facilitated comparative studies between the mouse model and human MASLD datasets.
Conclusions:
- * The LIDPAD model serves as a robust and reproducible preclinical tool for studying MASLD.
- * The model elucidates the role of the gut-pancreas axis in MASLD pathogenesis.
- * LIDPAD's fidelity to human MASLD supports its utility in advancing therapeutic development for this condition.
