Nonalcoholic Steatohepatitis (NASH) Model
Nonalcoholic Steatohepatitis (NASH) Model
Utilizing validated dietary, chemical, and combined metabolic induction protocols, our platform covers the full spectrum of disease progression—from simple hepatic steatosis and ballooning degeneration to active lobular inflammation and progressive pericentral/bridging fibrosis.
Indications & Applications
- In Vivo Efficacy Screening for NASH/MASH Therapeutics: Evaluation of novel small molecules, biologicals, GLP-1/GIP receptor agonists, and nuclear receptor modulators (e.g., FXR, THR-β, PPAR agonists).
- Anti-Steatotic & Lipid Metabolism Profiling: Screening candidates aimed at reducing intrahepatic triglyceride accumulation, enhancing mitochondrial fatty acid oxidation, and suppressing de novo lipogenesis (DNL).
- Anti-Inflammatory & Hepatoprotective Interventions: Validation of therapeutics targeting macrophage/Kupffer cell activation, inflammasome signaling, hepatocyte ballooning, and cell death pathways.
- Antifibrotic & Matrix Remodeling Screening: Efficacy testing of compounds targeting hepatic stellate cell (HSC) deactivation, extracellular matrix turnover, and advanced bridging fibrosis regression.
- Metabolic Syndrome & Comorbidity Evaluation: Profiling therapies addressing dual metabolic endpoints, including insulin resistance, dyslipidemia, and systemic glucose homeostasis.
Modeling Methodologies
1. Methionine- and Choline-Deficient (MCD) Diet Model
Feeding animals an MCD diet rapidly impairs VLDL secretion and lipid beta-oxidation. This induces severe macrovesicular steatosis, intense lobular inflammation, and rapid pericentral fibrosis within 4 to 8 weeks, serving as an accelerated screening platform for antifibrotic and anti-inflammatory candidates.
2. Choline-Deficient, L-Amino Acid-Defined, High-Fat Diet (CDAHFD) Model
Combines choline deficiency with high fat intake while maintaining methionine levels to prevent severe weight loss. Animals consistently develop hepatic steatosis, inflammation, and progressive pericentral to bridging fibrosis while preserving body mass stability, offering a highly reproducible system for chronic intervention studies.
3. High-Fat, High-Fructose, High-Cholesterol (HF/HF/HC or GAN/AMLN) Metabolic Model
Long-term administration of a nutrient-dense diet rich in saturated fats, fructose, and cholesterol induces authentic metabolic features of human MASH, including obesity, insulin resistance, dyslipidemia, hepatic steatofibrosis, and inflammatory infiltration over sustained study durations.
Clinical Relevance & Translation
- Histopathological Alignment: Replicates human NAFLD/NAS clinical scoring parameters, including zone 3 macrovesicular steatosis, lobular inflammation, and hepatocyte ballooning.
- Metabolic Phenotyping: Nutrient-dense diet platforms mimic the systemic metabolic syndrome baseline (obesity, hyperinsulinemia, dyslipidemia) commonly present in clinical MASH patient populations.
- Fibrotic Microenvironment: Captures hepatic stellate cell (HSC) transdifferentiation into myofibroblasts and the deposition of sinusoidal pericentral collagen septa.
Key Evaluation Endpoints
| Endpoint Domain | Specific Parameters & Assays | Pathological Significance |
|---|---|---|
| In Vivo & Systemic Metabolic Panels | • Body Weight & Food/Water Intake • Fasting Glucose & Oral Glucose Tolerance (OGTT) • Serum Insulin, Leptin & HOMA-IR Index |
Evaluates systemic metabolic syndrome features, obesity progression, and peripheral insulin sensitivity. |
| Serum Biochemistry & Liver Function | • ALT, AST, ALP • Total Cholesterol (TC) & Triglycerides (TG) • Non-Esterified Fatty Acids (NEFA) |
Quantifies active necroinflammatory injury, hepatic parenchymal damage, and systemic dyslipidemia. |
| Histopathology & Morphometry | • H&E (NAFLD Activity Score / NAS Grading) • Oil Red O & Biochemical Tissue TG/TC • Sirius Red / Masson (Collagen Volume Fraction - CVF) |
Provides clinical-grade scoring of steatosis, ballooning, lobular inflammation, and perisinusoidal fibrosis. |
| Molecular & Biomarker Analysis | • α-SMA, Collagen Type I, TIMP-1 • TNF-α, IL-1β, IL-6, MCP-1 • Lipid Peroxidation (MDA & Oxidative Stress) |
Tracks stellate cell transdifferentiation, matrix remodeling, macrophage recruitment, and hepatic inflammatory cascades. |
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