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Non-alcoholic steatohepatitis(NASH)Model

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of patients without a history of alcoholism. Non-alcoholic steatohepatitis (NASH) is a more serious form of NAFLD, which is not only manifested as fatty lesions of the liver, but also accompanied by intralobule inflammation, hepatocellular ballooning and fibrosis. The incidence of NAFLD is increasing year by year, and the incidence in China has reached around 15%. In recent years, the increase in the incidence of metabolic syndrome such as obesity and type 2 diabetes has further exacerbated the prevalence of NAFLD. NAFLD / NASH has become one of the top three causes of liver transplantation, which greatly threatens public health.

Preclinical animal model study is indispensable for the development of novel anti-NASH drugs. Gempharmatech provides drug developers with a variety of diet induced NASH mouse models for the drug efficacy study.

(1)Diet induced BKS-db model

①Study outline

Strain: Male BKS-db mice (7W)

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②Body weight 

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③Fasting blood glucose level was significantly increased in BKS-db mice fed 4 weeks of WD

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④ Plasma Chol and LDL-C level were significantly increased in BKS-db mice fed 4 weeks of WD

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⑤ Plasma ALT and AST level were significantly increased in BKS-db mice fed 4 weeks of WD

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⑥ Morphological evidence of fatty liver in BKS-db mice fed 4 weeks of WD


  
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⑦ Liver Chol and TG level were significantly increased in BKS-db mice fed 4 weeks of WD

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⑧ Histological evidence of NASH in BKS-db mice fed 4 weeks of WD

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*, Lipid droplet; Black arrow, intralobule inflammation; Black triangle, Ballooning. Scale bar=100μm (upper panel); 50μm (bottom panel).

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⑨ The expression level of biomarkers of inflammation and fibrosis were significantly increased in BKS-db mice fed 4 weeks of WD


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⑩ Efficacy Evaluation of MGL-3196

Ⅰ MGL-3196 significantly reduced the body weight gain of BKS-db NASH model

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Ⅱ MGL-3196 significantly relieved fatty liver in BKS-db NASH model

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Ⅲ MGL-3196 significantly reduced fasting blood glucose and plasma ALT level in BKS-db NASH model

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Ⅳ MGL-3196 significantly reduced plasma Chol and LDL-C level in BKS-db NASH model

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Ⅴ MGL-3196 significantly attenuated the hepatic steatosis, inflammation and ballooning in BKS-db NASH model

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*, Lipid droplet; Blue triangle, Ballooning; Red triangle, inflammation. Scale bar=50μm.

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Ⅵ MGL-3196 reduced the expression level of biomakers of lipid storage, inflammation and fibrosis in BKS-db NASH model 

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(2)B6 Alms1 KO NASH model

B6 ALMS1 KO mouse modle has severe metabolic syndrome. Induction of 8w B6 ALMS1 KO mice with western diet accelerates the development of Nash.

(1) 4 weeks of WD feeding further elevated the plasma Chol and LDL-C level of B6 Alms1 KO mice

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(2) 4 weeks of WD feeding significantly increased the plasma ALT and AST level of B6 Alms1 KO mice

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(3) 6 weeks of WD feeding induced fatty liver in B6 Alms1 KO mice

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(4) 6 weeks of WD feeding significantly increased liver TG and Chol content of B6 Alms1 KO mice

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(5)Histological evidence of NASH in B6 Alms1 KO mice fed 6 weeks of WD

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*, Lipid droplet; Blue arrow, inflmmation; Black arrow, Fibrosis. Scale Bar=50μm.


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(6) Comparison of classic NASH model and B6 Alms1 KO NASH model

(3) Classic HFD+CCl4 NASH model

①Study outline

Strain: Male C57BL/6J mice (6W)

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②INT-747 significantly attenuated hepatic steatosis and fibrosis of HFD+CCl4 NASH model

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Data were presented as Mean±SD. n= ****, P<0.0001 by one way ANOVA with Dunnett’s post hoc test.

(4)Special diets induced NASH model

Histological evidence of NASH in mice fed different special diets

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*, Lipid droplet; Black arrow, inflammation; Yellow arrow, Ballooning; Blue arrow, Fibrosis. Scale Bar=50μm.

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(5)Comparison of NASH models

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Time:2020-12-28