Non-Alcoholic Fatty Liver Disease (NAFLD) Model

• In Vivo Efficacy Screening for NAFLD/MASLD Candidates: Evaluation of small molecules, RNA-based therapeutics, GLP-1/GIP/Glucagon receptor co-agonists, PPAR modulators, and SGLT2 inhibitors.
• Anti-Steatotic & Lipid Homeostasis Profiling: Screening compounds designed to inhibit de novo lipogenesis (DNL), enhance mitochondrial β-oxidation, or reduce hepatic triglyceride (TG) accumulation.
• Insulin Sensitizers & Glucose Regulators: Pharmacodynamic validation of agents improving systemic and intrahepatic insulin sensitivity, glucose tolerance, and metabolic homeostasis.
• Prevention of NASH/MASH Disease Progression: Early-stage interventional studies assessing whether novel candidates can arrest the transition from simple steatosis to necroinflammation.
• Nutraceutical & Dietary Supplement Testing: Functional validation of novel food components, natural extracts, and metabolic health formulations in robust animal models of diet-induced obesity.

1. High-Fat Diet (HFD, 45% or 60% kcal Fat) Model

Sustained feeding of rodents with high-fat diets over 8 to 16 weeks results in gradual body weight gain, visceral adiposity, hyperinsulinemia, and diffuse macrovesicular hepatic steatosis, serving as the gold standard for diet-induced metabolic obesity and NAFLD.

2. Western Diet (High-Fat / High-Fructose / High-Cholesterol) Model

Combines dietary fat and cholesterol with sugar-sweetened drinking water (fructose/glucose). Fructose bypasses hepatic phosphofructokinase regulation, rapidly stimulating de novo lipogenesis, inducing severe hepatic steatosis, elevated liver enzymes, and early oxidative stress.

3. Monogenic & Combined Genetic/Dietary Models (ob/ob, db/db, ZDF)

Utilizes leptin-deficient (ob/ob) or leptin receptor-deficient (db/db, ZDF) strains that spontaneously develop severe hyperphagia, profound obesity, type 2 diabetes, and pronounced hepatic steatosis. Combining genetic models with high-fat feeding accelerates disease phenotyping.