Metabolism

Nonalcoholic Steatohepatitis (NASH) Models

Biocytogen has established various types of induced NASH mouse models, such as the Gubra-Amylin (GAN) diet / GAN+CCL4 induced NASH mouse model, the High Fat Methionine Choline Deficiency (HFMCD)-induced NASH mouse model, and the STAM-NASH mouse model.

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  • NASH Model Introduction
  • Results

Publication

    NASH Model Introduction

    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.

    • Carbon tetrachloride (CCl4): CCl4 injection causes significant liver inflammation and fibrosis.
    • Gubra-Amylin (GAN): 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.
    • STAM: Neonatal mice injected with Streptozotocin and fed a high fat diet exhibited altered body weight and blood glucose levels.

    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

    Results
    GAN diet+CCL4 Induced NASH Mouse Model

    MGL3196 and OCA alleviated NASH symptom in GAN diet+CCL4 induced NASH mouse model. A-B, ALT and AST levels of modeling and treatment group. C-F, TG, TC, HDL-C, LDL-C levels of modeling and treatment group. Data are expressed as mean ± SEM. N = 9 mice per group. *p<0.05, **p<0.01,***p<0.001.

    Resmetirom and OCA treatment alleviates symptoms of NASH

    Resmetirom and OCA decreased NAS scores. A, Representative pictures of H&E staining showing degree of NASH. B, NAFLD activity score (NAS) assessed by an external expert pathologist. C-D, TG and TC content in liver after treatment. Data are expressed as mean ± SEM. N = 9-10 mice per group. *p<0.05, **p<0.01, ***p<0.001.

    Resmetirom and OCA treatment alleviates liver fibrosis

    Resmetirom and OCA treatment alleviates liver fibrosis. A, Representative pictures of Sirius Red staining showing degree of liver fibrosis (scare bar：200μm). B, Liver fibrosis score was assessed according to Sirius Red staining. C, Representative pictures of IHC staining showing α-SMA expression (scare bar：200μm).D, Quantitively data of α-SMA expression. Data are expressed as mean ± SEM. N = 9 mice per group. *p<0.05, **p<0.01,***p<0.001,****p<0.0001.