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Metabolic Dysfunction-Associated Steatohepatitis (MASH) Animal Model

Metabolic Dysfunction-Associated Steatohepatitis (MASH) Animal Model

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Metabolic Dysfunction-Associated Steatohepatitis
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Model Introduction

Model Introduction

Platform Service Advantages

Platform Service Advantages

Experimental results

Experimental results

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Metabolic Dysfunction-Associated Steatohepatitis

Introduction to the MASH Animal Model

Metabolic dysfunction‑associated steatohepatitis (MASH, formerly known as non‑alcoholic steatohepatitis, NASH) is classified under the umbrella of non‑alcoholic fatty liver disease (NAFLD) and represents a group of progressive metabolic liver disorders. The hallmark features include hepatic steatosis, inflammatory responses, hepatocellular injury, and liver fibrosis; if left unchecked, the condition may progress to cirrhosis and even give rise to hepatocellular carcinoma. Obesity, insulin resistance, and type 2 diabetes markedly increase the risk of developing MASH and accelerate disease progression.

To meet the needs of drug discovery and mechanistic studies, we can flexibly control the endpoint of model induction, offering MASH animal models with or without fibrosis. We also provide comprehensive downstream pathway‑level analyses, including, but not limited to, key targets in the AMPK/ACC, NF‑κB, and TGF‑β1/Smad pathways.

To accurately model the critical steps in the progression from metabolic syndrome to liver cirrhosis, we employed the widely recognized composite diet‑induced method. In addition to overt phenotypic features such as markedly rounded body shape, abdominal distension, and increased resistance to grasping, we established rigorous biochemical and metabolic reference standards.

Service Advantages of Aniphe BioLab’s MASH Animal Model Platform

Leveraging experience from thousands of MASH model‑building projects, we achieve a modeling success rate exceeding 95%. We implement rigorous in‑batch quality control and stringent inclusion criteria, providing a rapid and reliable in vivo solution for your drug discovery and preclinical efficacy evaluation.

Comprehensive model coverage

Model stability

Thousands of model‑building projects, with a success rate exceeding 95%.

Standardization of the modeling process

Quality control of the same batch

Random sampling was used to assess body weight, four lipid parameters, and ultrasound elastography, ensuring phenotypic homogeneity prior to enrollment.

Multidimensional Evaluation System

Strictly selected for enrollment

Ensure that the body weight differences within each experimental group are less than 10% to maintain statistical power.

Adaptable to multi-cycle studies

Predictive efficacy

By employing a comprehensive disease‑progression model, it is possible to predict in advance the therapeutic efficacy of drugs across the distinct stages of inflammation, steatosis, and hepatic fibrosis, thereby reducing the rate of clinical trial failure.

Standardization of Data Delivery

Fast and stable

A rapid and stable in vivo solution.

Modeling cycle

6–8 weeks

1  Laboratory animals

C57BL/6J male mice

1  Positive drug

There is no specific positive drug; obeticholic acid may be considered: a potent agonist of the Farnesoid X Receptor (FXR). By modulating bile acid metabolism and inhibiting hepatic stellate cell activation, it significantly improves liver inflammation and fibrosis scores.

1  Application areas

NASH drug development, research on the mechanisms of hepatic fibrosis, validation of therapeutic targets, studies of metabolic liver diseases, type 2 diabetes, and more. NASH is a severe progressive form of NAFLD, characterized by hepatocellular steatosis, lobular inflammation, and ballooning degeneration, with or without fibrosis. This model is designed to replicate the key pathological steps in the human progression from metabolic syndrome to cirrhosis.

Experimental results

Construction of the MASH animal model

Methods: Induction by a high-fat diet combined with a high-fat, high-fructose, and high-cholesterol diet.

Source of the method: Asgharpour, Amon et al. “A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer.” Journal of Hepatology, vol. 65, no. 3 (2016): 579–588. doi:10.1016/j.jhep.2016.05.005

Validation of a diet‑induced MASH mouse model of hepatic injury

Metabolic abnormalities: Following the induction of the model by switching to a high-fat diet, blood glucose levels in the model group mice were significantly elevated. Intraperitoneal glucose tolerance testing (IPGTT) revealed that, even 2 hours after glucose administration, blood glucose remained above baseline, and the area under the curve was markedly greater than that of the control group mice.

Liver Injury and Lipid Metabolism Disorders: Serum biochemical assays revealed that, compared with the blank control group, the model‑group mice exhibited significantly elevated levels of ALT and AST, indicating marked hepatic damage. Meanwhile, serum concentrations of TG, TC, LDL‑c, and HDL‑c were also markedly increased relative to the blank control group, suggesting dyslipidemia in the NASH mice.

 

 

Levels of TG, TC, LDL‑c, HDL‑c, ALT, and AST in the serum of mice from the NASH model group and the control group. Data are presented as Mean ± SD (n = 3). p* < 0.05, p** < 0.01, p*** < 0.001, p**** < 0.0001.

ZST+ Domain Light Ultrasound: Noninvasive Dynamic Monitoring of Drug Efficacy in Liver Fibrosis

Traditionally, assessing liver fibrosis has required end-point histological sampling, which not only consumes experimental animals but also precludes the acquisition of longitudinal data from individual mice before and after treatment. To address this limitation, we have implemented in vivo imaging using the ZST plus domain‑light high‑frequency ultrasound system for animal studies. This platform leverages three core technologies to overcome the drawbacks of conventional linear scanning and manual pressure: domain scanning and domain processing harness the mouse’s intrinsic physiological pulsations to quantify tissue deformation, thereby minimizing human error; domain focusing is tailored to the size of the mouse liver, enhancing image resolution; and, combined with natural strain elastography, it delivers objective, quantitative strain‑ratio measurements, enabling continuous, in vivo evaluation of hepatic stiffness with more robust and reliable data.

Ultrasound results showed that, as the modeling period progressed, the hardness histogram of the model group shifted significantly toward the high‑hardness (Hard) region, and the strain ratio increased markedly in a time‑dependent manner, objectively quantifying and reproducing the progressive pathological process of hepatic fibrosis. This not only closely corresponded to the collagen fiber deposition area assessed at the endpoint but also enabled researchers to dynamically monitor the effects of pharmacological interventions in real time, without sacrificing the animals.

 

 

Evolution of Liver Stiffness on Ultrasound Elastography in MASH Mice from 16 to 36 Weeks of Age

Pathological gold standard at the endpoint: from qualitative observation to quantitative scoring

Whether the model was successfully established ultimately depends on the pathological gold standard. We performed a comprehensive series of histopathological analyses to validate the model mice:

H&E staining: In the model group, hepatocyte arrangement was disorganized, with numerous round vacuoles observed in the cytoplasm; hepatocytes also exhibited marked swelling and rounding (ballooning degeneration), reflecting typical hepatocellular injury and steatosis.

Oil Red O staining: Hepatocytes in the model group were filled with numerous, densely packed bright red lipid droplets, confirming severe steatosis.

Masson’s trichrome staining: In the model group, prominent blue‑stained deposits were observed in the hepatic cords and around the central veins, clearly confirming the occurrence of hepatic fibrosis and indicating that the model has progressed to the fibrotic stage.

 

 

Multiple pathological staining techniques confirmed that NASH model mice exhibit steatosis and hepatic fibrosis.

Advanced Delivery Standards

In addition to intuitive histopathological images, we provide NAS‑score–based quantitative data that meet international standards—assessing steatosis, lobular inflammation, and ballooning—and perform rigorous fibrosis staging (F0–F4), thereby furnishing robust, statistically valid evidence for your pharmacological efficacy evaluations.

 

 

The NAS scoring system consists of three components: ① hepatocellular steatosis (0–3 points); ② lobular inflammation (0–3 points); and ③ ballooning degeneration (0–2 points), with a total score ranging from 0 to 8. A NAS score <3 is classified as non‑NASH; a NAS score >4 is classified as NASH; and a NAS score between 3 and 4 indicates a possible diagnosis of NASH.