Introduction to Metabolic Disease Modeling
Nonalcoholic fatty liver disease (NAFLD) broadly represents multiple disorders and is marked by excessive fat accumulation in the liver, independent of heavy alcohol consumption. In addition to a fatty liver, there are several pathological changes associated with NAFLD, including hepatitis, hepatocyte injury, fibrosis and liver scar formation, which may lead to cirrhosis or liver cancer. While the mechanism of nonalcoholic steatohepatitis (NASH) progression is not clear, the co-existence of type II diabetes and NAFLD increases the risk of developing NASH.
The clinical symptoms of NASH are complex and include obesity, insulin resistance, steatohepatitis, hepatocyte ballooning, and fibrosis. Animals used in preclinical experiments to model NASH are either genetically modified, diet-induced, or a combination of the two.
While it is challenging to mimic all the pathological features of human disease, to understand the mechanisms underlying NASH induction and progression, and to develop innovative therapies, we established several mouse models representing different stages of NASH pathogenesis.
- Western diet (WD): This high fructose and high cholesterol diet-induced NASH model develops obesity, impaired glucose tolerance and hepatic steatosis.
- High-fat methionine-choline-deficient diet (HFMCD): This diet contains 60 kcal% fat and is deficient in methionine and choline. HFMCD-induced NASH model shows increased liver injury, hepatic steatosis, and fibrosis accompanied by increased NAS scores.
- Carbon tetrachloride (CCl4): CCl4 injection causes significant liver inflammation and fibrosis.
Each model described slightly differs in the phenotype observed. Our experts will help you select the appropriate model currently available according to the characteristics of the target.
CCl4 induced NASH mouse…
A well-established and widely accepted experimental mouse model to study liver fibrosis and cirrhosis is via Carbon tetrachloride (CCl4) injection. In many aspects, CCl4-induced hepatic…Learn More
Western Diet induced NASH…
Well-established NAFLD/NASH mouse models successfully induce fibrosis, but struggle to recapitulate the full complexity of human disease, which often presents signs of metabolic syndrome (MS).…Learn More
HFMCD induced NASH mouse…
The high-fat methionine-choline-deficient diet (HFMCD) is a classic model for NASH induction, which consists of a 60 kcal% fat, methionine and choline-deficient diet. Both methionine…Learn More