Development and Characterization of a High-Fat High-Sucrose Dietary Model for Experimental Hepatic Injury in Wistar Rats

Background:

Excessive consumption of dietary fat and simple sugars is associated with dyslipidemia, hepatic lipid accumulation, oxidative stress and chronic inflammation, contributing to metabolic liver disease. A standardized dietary model is important for investigating diet-associated hepatic injury in preclinical research.

Objective:

This study aimed to formulate and characterize a high-fat high-sucrose (HFHS) diet and evaluate its potential to induce metabolic and hepatic alterations in Wistar rats.

Methods:

An HFHS diet pellets was formulated using selected nutritional ingredients in defined proportions and evaluated for physical and nutritional characteristics. The formulation exhibited hardness of 10.91 ± 0.28 kg/cm² and friability of 0.80 ± 0.05%. Twelve male Wistar rats were divided into normal control (n=6) and disease control (n=6) groups. The disease group received the HFHS diet for 8 weeks. Body and liver weights, liver index, lipid profile, hepatic enzymes, oxidative stress markers, inflammatory mediators and hepatic triglycerides were assessed. Liver histopathology was also performed.

Results:

HFHS-fed rats showed increased body weight, liver weight/liver index, total cholesterol, triglycerides, LDL-C, ALT, AST and ALP, with decreased HDL-C. MDA/TBARS and oxidative stress increased, whereas SOD, catalase and GSH decreased. TNF-α, IL-6 and MCP-1 levels and hepatic triglyceride accumulation were increased. Histopathology revealed hepatic steatosis, hepatocellular ballooning, inflammatory infiltration, sinusoidal dilatation, vascular congestion and focal hepatocellular necrosis.

Conclusion:

The formulated HFHS diet produced dyslipidemic, oxidative, inflammatory and histopathological alterations after 8 weeks, demonstrating its potential as a reproducible preclinical model of diet-associated hepatic injury.