Hypoxia aggravates non-alcoholic fatty liver disease in presence of high fat choline deficient diet: a pilot study

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.