HFHF-induced Liver Fibrosis

Effect of test article on High Fat and High Fructose (HFHF)-induced Liver Fibrosis

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Overview

Liver fibrosis represents a classical outcome of many chronic liver diseases irrespectively of the etiology of injury. It results from successive rounds or chronic activation of the physiological wound-healing response that sustains persistent fibrogenesis and leads to progressive fibrosis of the organ through inflammation or reactive oxygen species mechanism.

Compliance

Non-GLP compliant. The study is best suited to demonstrate efficacy in discovery-phase preclinical development strategies.

Purpose of the Study

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. 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. The aims of this study would be to demonstrate the efficacy of test article during prophylaxis or therapeutic intervention.

Parameters Monitored

  • 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

Study Timeline

  • One week to finalize the protocol/formulation
  • In vivo disease development phase: 16 weeks
  • Terminal surgery and acquisition: 1 day of surgery per experimental group
  • Analysis of biomarkers parameters: 7 days
  • Morphometric and histopathological examination: 14 days following reception of the slides

Reporting

Non-audited report 2 weeks following the last functional measurement.