High-Fat Diet-Induced Obesity in Rodents: Dietary Composition, Adipose Remodeling and Metabolic Dysfunction: A Comprehensive Review

High-fat feeding is widely used to model diet-associated obesity and metabolic dysfunction in rodents, but "high-fat diet" does not describe a single reproducible exposure. The phenotype depends on the percentage of energy from fat, fatty-acid source, carbohydrate and protein composition, energy density, comparator diet, animal strain and substrain, sex, age, and exposure duration. These variables affect energy intake and expenditure as well as adiposity, glucose regulation, circulating lipids, liver pathology, and inflammatory readouts. Available comparative studies show that changing fat source can alter adipose distribution and metabolic outcomes even when diets are similarly fat-rich, while strain and sex can modify susceptibility and the time course of disease.[3,4,93] Consequently, body weight alone is an inadequate validation criterion. Robust studies should report exact diet composition and energy density, measure both food and energy intake, characterize body composition and tissue pathology, and prespecify metabolic endpoints. Rodent HFD models are useful for mechanistic experiments, but their controlled setting and biological heterogeneity limit direct extrapolation to human obesity.[1] This narrative review synthesizes the supplied outline and reference collection; it is not a protocol-driven systematic review.