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Updated: Dec 9, 2025
The Murine Choline-Deficient, Ethionine-Supplemented CDE Diet Model of Chronic Liver Injury
Published on: October 21, 2017
Hypoxia aggravates non-alcoholic fatty liver disease in presence of high fat choline deficient diet: A pilot study
Soumalya Sarkar1, Sankarsan Bhattacharya1, Md Jahangir Alam1
1Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad 121001, Haryana, India.
Aim:
NAFLD is a chronic and progressive disease for which there are no FDA-approved drugs available in the market. Drug discovery is a time-consuming procedure and requires screening of hundreds of small molecules to find new chemical entities (NECs) for a particular disease. Current preclinical NAFLD animal models take a longer time, which enhances the duration and expenses of the screening procedure. Hence to shorten the duration, we have proposed a preclinical animal model for rapid induction of non-alcoholic steatohepatitis (NASH), an advanced stage of NAFLD in rats.
Methodology:
The animals were divided into three groups; control, high fat choline deficient (HFCD) and high fat choline deficient diet with sodium nitrite (40 mg/kg b.w. i.p. per day) (HFCD + NaNO2) respectively. Four weeks later physical and serum biochemical parameters were assessed, intraperitoneal glucose tolerance test was performed, and histopathology and gene expression were analysed.
Key Findings:
Hypoxic stress aggravates the lipid accumulation, ballooning, lobular inflammation and fibrosis in hepatic tissue in presence of HFCD diet.
Significance:
This novel rodent model could be a useful NAFLD model to screen small molecules rapidly for treatment of NASH.
Insights
A new rat model rapidly induces non-alcoholic steatohepatitis (NASH), an advanced form of non-alcoholic fatty liver disease (NAFLD). This model accelerates the screening of potential drugs for NASH treatment.
Area of Science:
- Hepatology
- Pharmacology
- Animal Models
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a chronic condition lacking FDA-approved treatments.
- Drug discovery for NAFLD is lengthy, involving extensive screening of small molecules.
- Current preclinical NAFLD models are time-consuming, increasing drug development costs.
Purpose of the Study:
- To develop a rapid preclinical animal model for non-alcoholic steatohepatitis (NASH), an advanced stage of NAFLD.
- To shorten the duration and reduce the expenses associated with NAFLD drug screening.
Main Methods:
- Rats were divided into control, high-fat choline-deficient diet (HFCD), and HFCD with sodium nitrite groups.
- After four weeks, physical and serum biochemical parameters were assessed.
- Intraperitoneal glucose tolerance tests, histopathology, and gene expression analysis were performed.
Main Results:
- The high-fat choline-deficient diet (HFCD) combined with sodium nitrite induced NASH.
- Hypoxic stress exacerbated lipid accumulation, ballooning, lobular inflammation, and fibrosis in hepatic tissue.
- This model effectively demonstrated the pathological features of NASH.
Conclusions:
- A novel rodent model for rapid NASH induction has been established.
- This model is suitable for accelerating the screening of small molecules for NASH treatment.
- The model provides a valuable tool for NAFLD drug discovery research.
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