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.

Charles-E. Laurent

Ph.D., Director of In-Vivo Pharmacology

“Over the past 13 years, I had the greatest opportunity to exploit my passion for science at IPST by contributing to the design, and validation of unique assays which are now routinely run and serve to quantify the efficacy in preclinical drug candidates. My greatest contribution was to see the increase in demand for efficacy services such as the rodent model of pulmonary arterial hypertension (PAH), as well as our intravascular thrombosis and hemostasis models.” Charles completed his doctorate in Pharmacology at the Université de Montreal followed by 4 years of post doctorate studies at the University of Pittsburgh in the Department of Molecular Genetics and Biochemistry. His field of expertise includes cardiovascular pharmacology and molecular biology.