An Indian Diet Relevant Rat Screening Model for Hypertriglyceridemia Associated Fatty Liver

Abstract

Hypertriglyceridemia is a dominant and early metabolic abnormality underlying fatty liver disease in Indian populations, often preceding obesity, insulin resistance, or inflammatory liver injury. Many diet-induced rodent models of hepatic steatosis rely on extreme obesogenic or fructose-rich diets that poorly reflect real-world Indian dietary patterns. Here, we describe a diet-induced rat screening model designed to reflect typical Indian cereal-rich, visible-fat dietary exposure and to preferentially induce triglyceride-centric hepatic lipid accumulation. The model reproducibly induces hepatic triglyceride deposition with preserved liver architecture and minimal inflammatory features, aligning with early-stage fatty liver observed clinically in Indian patients. This work does not propose a novel disease model nor evaluate therapeutic efficacy, but establishes a translationally relevant screening tool for prioritizing lipid-modulating interventions in hypertriglyceridemia-associated fatty liver. We show that the high-fat diet increased serum triglycerides [~]1.8 -fold versus chow (normalized index 1.0 vs 1.8), with organ weights remaining within [~]0.95-1.00 of reference (normalized indices), supporting screening tolerability. Secondary changes in liver morphology and histopathology were indicative of fatty liver.