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Effects of D4-MASLD and D5-MASLD Diets on Rats: Pathway Alterations Similar to Human MASLD

ABSTRACT: Animal models are essential to understand the mechanisms underlying the onset and progression of metabolic associated steatotic liver disease (MASLD), a rapidly growing form of chronic liver disease driven largely by the global rise in metabolic syndrome. However, existing animal models for MASLD often fail to accurately reproduce advanced human liver disease, and have varying degrees of clinical relevance. To address this, we have undertaken efforts to create a dietary translational model of MASLD in rats that closely replicates the full MASLD phenotype observed in humans, including advanced fibrosis, portal hypertension, and metabolic syndrome. Three MASLD rat models were developed by sequentially combining a high-fat glucose-fructose diet (HFGFD) with additional factors: lipopolysaccharide, increased cholesterol (Chol), and cholic acid (CA) at different concentrations. Of these, two diets—D4-MASLD (HFGFD + 2% Chol) and D5-MASLD (HFGFD + 2% Chol + 0.1% CA)—effectively replicated MASLD characteristics. Transcriptomic analysis revealed that while both diets significantly altered gene expression compared to controls, D5-MASLD had a greater impact on the activation of inflammation and immune response pathways. The inclusion of CA in D5-MASLD exacerbated pathways related to microbiota changes, intestinal barrier dysfunction, and bacterial translocation. Additionally, comparison of the transcriptomic profiles of these diet-induced rat models with data from MASLD/MASH patients further validated the relevance of these models, establishing a robust platform for studying MASLD pathogenesis and evaluating potential therapeutic interventions.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE282001 | GEO | 2026/04/20

REPOSITORIES: GEO

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Effects of D4-MASLD and D5-MASLD Diets on Rats: Pathway Alterations Similar to Human MASLD

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