Animal models have been indispensable in advancing understanding of the mechanisms underlying human obesity, by providing a controlled framework in which genetic, environmental, and behavioral determinants of disease risk can be systematically examined. Rodents have been widely used, due to their well-characterized genomes, short reproductive cycles, and suitability for genetic manipulation. Seminal discoveries regarding appetite regulation and energy homeostasis emerged from murine models, perhaps most notably the ob/ob mouse, lacking the gene encoding leptin, which develop profound obesity and metabolic disturbances. Further work using rodents has elucidated the interplay between neuroendocrine circuits, adipose tissue, and peripheral metabolic organs, thereby providing insights into the pathophysiology of obesity-related conditions such as type 2 diabetes and non-alcoholic fatty liver disease. Diet-induced obesity (DIO) models have also been widely utilized to replicate human obesogenic environments. Feeding rodents high-fat or high-sugar diets induces weight gain, insulin resistance, and systemic inflammation, thereby recapitulating the metabolic syndrome observed in humans. Such approaches have clarified how nutrient excess disrupts cellular signaling pathways and contributes to chronic low-grade inflammation. Nonhuman primates share physiological and behavioral similarities with humans, particularly in fat distribution and diet-related pathologies, making them valuable for translational studies. Zebrafish, despite their evolutionary distance, have proven useful for high-throughput metabolic studies.
Nevertheless, animal models have limitations. No single model fully captures the complexity of human obesity, which is influenced by cultural, psychological, and socioeconomic factors impossible to recapitulate in laboratory settings. Rodent metabolism, for example, differs from humans in aspects of fat distribution, thermogenesis, and gut microbiota, potentially limiting translational scope. Thus, animal models remain fundamental to obesity research, offering critical insights into genetic, metabolic, and behavioral drivers of disease, while facilitating the development and testing of therapeutic strategies. Despite their shortcomings, they constitute an essential component of translational obesity research.