HFHF-induced Liver Fibrosis
Purpose
The HFHF diet is a novel model to induce insulin resistance and NASH with a fibrosis progression. HFHF represents occidental nutritional status based on fat and sugar consumed daily in modern societies. The aim of this study would be to demonstrate the efficacy of test article during prophylaxis or therapeutic intervention.
Method
Since the liver is the only organ capable of managing fructose and is immediately metabolized into fat, this model rapidly increases triglyceride content into the liver and generates lipid metabolism alterations, with an aberrant accumulation of triglycerides, mitochondrial dysfunction, inflammation, and oxidative stress.
Study outcome
- Insulin resistance markers (Glucose, insulin, HOMA-IR, NEFA, TG)
- Plasmatic liver inflammation biomarkers (ALP, ALT, ASP, bilirubin)
- Liver oxidative stress marker (MDA, lipid peroxidation)
- Liver inflammation marker (TNF-alpha)
- Histopathology of formalin-fixed and paraffin-embedded liver section
- H&E staining for morphology and steatosis
- Masson’s trichrome for fibrosis
- Sirius red for collagen content
Compliance
Non-GLP compliant. The study is best suited to demonstrate efficacy in discovery-phase preclinical development strategies.