High-Fat & High-Cholesterol Diet induced Non-Alcoholic Steatohepatitis (NASH) Modeling & Pharmacodynamics Service

Creative Biolabs provides a variety of well-established animal models to evaluate drug efficacy for NASH, helping researchers screen potential therapies and better understand the underlying mechanisms of the disease.

Introduction

Non-alcoholic steatohepatitis (NASH) is a progressive liver disease that is part of the spectrum of non-alcoholic fatty liver disease (NAFLD). It is characterized by excessive fat accumulation in the liver, inflammation, and hepatocyte damage, which can lead to fibrosis, cirrhosis, and even liver cancer. NASH is often associated with metabolic risk factors such as obesity, type 2 diabetes, dyslipidemia, and insulin resistance. It is a major cause of liver-related morbidity and mortality worldwide. Unlike alcoholic liver disease, NASH occurs in individuals who consume little or no alcohol, making it a growing public health concern, particularly in industrialized nations. As NASH can remain asymptomatic in the early stages, it is often diagnosed when liver damage is already advanced. Early intervention is crucial to prevent the progression to cirrhosis and liver failure. Given the complex pathophysiology of NASH, including insulin resistance, inflammation, and oxidative stress, developing effective therapeutic options remains a significant challenge.

Disease Models and Applications

The High-Fat & High-Cholesterol Diet induced NASH model is a widely used method to replicate human NASH pathology in rodents. This model is established by feeding animals a diet high in fat and cholesterol for an extended period, leading to liver fat accumulation, inflammation, and eventual fibrosis. The key features of this model include the development of hepatocyte ballooning, steatosis, and varying degrees of liver fibrosis, which are crucial for simulating human NASH. This model allows for the investigation of the disease's progression and the evaluation of various therapeutic strategies. The advantages of this model include its reproducibility and relevance to human NASH, while a potential drawback is the need for long-term feeding protocols that may not always mimic the rapid onset seen in some human patients.

• Simulates: The High-Fat & High-Cholesterol Diet induced NASH model simulates key pathological features of human NASH, including steatosis, hepatocyte ballooning, inflammation, and fibrosis, closely reflecting the disease's progression.
• Evaluates Drugs: This model is used to evaluate drug candidates targeting liver inflammation, fibrosis, and lipid metabolism, as well as those that address insulin resistance and metabolic dysfunction. It is ideal for screening potential therapies for NASH, including anti-inflammatory agents, antioxidants, and drugs aimed at liver fibrosis reduction.

Fig. 1 Representative images of p62 immunostaining of samples from SHRSP5/Dmcr rats fed control and HFC diets for 2 and 8 weeks.¹

Measurements

For the High-Fat & High-Cholesterol Diet induced NASH Model, we provide comprehensive measurements to assess disease progression and evaluate drug efficacy, including:

• General observations: Body weight, liver weight, mortality rate, stool consistency, and gastrointestinal bleeding.
• Histological analysis: Liver histology to assess steatosis, hepatocyte ballooning, and fibrosis using Hematoxylin and Eosin (H&E) staining.
• Cytokine profiling: ELISA assays for inflammatory mediators such as TNF-α, IL-6, and IL-1β to evaluate inflammatory response.
• Liver enzyme levels: Serum biomarkers such as ALT, AST, and alkaline phosphatase to assess liver injury.
• Gene and protein expression: RT-qPCR and Western blot techniques for profiling markers of inflammation, fibrosis, and lipid metabolism.

These methods ensure accurate assessment of drug efficacy and the disease's pathological features.

Related Services

In addition to the High-Fat & High-Cholesterol Diet induced NASH model, we also offer NASH models induced through other dietary and chemical approaches. Each method has its unique advantages depending on the research focus, such as faster onset or specific liver injury mechanisms. Our team will work closely with you to select the most appropriate model for your study.

• Diet induced Obesity (DIO) Mouse NASH Model
• High-Fat Diet induced NASH Model
• Methionine Choline-Deficient (MCD) Diet induced NASH Model
• Choline-Deficient L-Amino Acid-Defined (CDAA) Diet induced NASH Model
• High-Fat & High-Carbohydrate Diet induced NASH Model
• High-Fat & High-Cholesterol Diet & Fructose induced NASH Model
• High-Fat & Fructose induced NASH Model
• Diethylnitrosamine (DEN) & High-Fat & High-Carbohydrate Diet induced NASH Model
• High-Fat & CCL₄ induced NASH Model
• Streptozotocin (STZ) & High-Fat induced NASH Model
• MC4R KO Mouse Model
• LDLR KO Mouse Model

Advantages

• Comprehensive Expertise: Our team offers extensive experience in developing and customizing NASH models tailored to specific research needs.
• Advanced Technology: We utilize cutting-edge technologies for disease assessment, ensuring highly accurate results.
• Custom Solutions: We provide expert consultation in experimental design, model selection, and data analysis to meet your research objectives.
• High Reproducibility: Our NASH models are designed for reproducibility, ensuring reliable and consistent results across studies.
• Broad Drug Screening Capability: We offer a wide range of preclinical models for evaluating various drug candidates, from anti-inflammatory to anti-fibrotic therapies.

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FAQs

1. Q: What is the difference between NASH models and NAFLD models?

   A: NASH models specifically involve liver inflammation and fibrosis, while NAFLD refers to simple fat accumulation without significant inflammation or liver damage.

2. Q: How long does it take to develop a NASH model using a high-fat diet?

   A: The High-Fat & High-Cholesterol Diet induced NASH model typically requires 8-12 weeks for significant disease progression to occur.

3. Q: What are the most common drugs tested in NASH models?

   A: Common drugs tested include anti-inflammatory agents, antioxidants, and agents targeting liver fibrosis and metabolic dysfunction.

4. Q: Can this model be used for drug safety studies?

   A: Yes, the model is suitable for both efficacy and safety evaluations, including assessing potential liver toxicity and adverse effects.

5. Q: Do you provide data analysis services?

   A: Yes, our scientific team offers full data analysis services to assist in interpreting results and guiding the next steps in your research.

Published Data

Fig. 2 Electron microscopic image.¹

Electron microscopy revealed the presence of giant lysosomes, which are not typically observed, along with an accumulation of autophagosomes, an atypical finding, in the livers of rats from the 8-week High-Fat-Cholesterol (HFC) diet group (Fig. 2). These autophagosomes were associated with autologous cells exhibiting heterochromatin, which adhered to the nuclear membrane. In contrast, the livers of rats from the 8-week control diet group displayed normal lysosomes with vacuolar degeneration, characteristic of non-pathological conditions.

Reference

1. Naito, Hisao et al. "High-fat and high-cholesterol diet decreases phosphorylated inositol-requiring kinase-1 and inhibits autophagy process in rat liver." Scientific Reports vol. 9,1 12514. 29 Aug. 2019, DOI:10.1038/s41598-019-48973-w. Distributed under an Open Access license CC BY 4.0, without modification.

For Research Use Only.