Comprehensive Insights into Obesity: Etiology, Risk Factors, Pathophysiology and Interventions through In vitro, In vivo and In silico Models

Obesity is a multifactorial, chronic disease characterized by abnormal or excessive fat accumulation arising from prolonged energy imbalance. It is strongly associated with an increased risk of metabolic, cardiovascular, and neoplastic disorders, thereby constituting a major global health burden. The pathogenesis of obesity involves complex mechanisms, including adipocyte hypertrophy and hyperplasia, dysregulated lipid metabolism, and chronic low-grade inflammation, further influenced by genetic predisposition, behavioral patterns, and environmental factors. Epidemiological data reveal alarming prevalence trends, with more than one third of the global population considered as overweight or obese. Conventional management strategies such as lifestyle modification, pharmacotherapy, and bariatric surgery are limited by suboptimal efficacy and poor long-term sustainability, highlighting the urgent need for more effective therapeutic approaches. This review emphasizes recent advances in the cellular and molecular understanding of obesity, with a focus on adipogenesis and adipose tissue dysfunction as critical therapeutic targets. Particular attention is directed toward the complementary use of in vitro, in silico, and in vivo models in antiobesity drug discovery. In vitro assays, including pancreatic lipase inhibition and adipocyte differentiation studies, provide mechanistic insights into adipose biology. In silico approaches, such as molecular docking and molecular dynamics simulations, enable the prediction of molecular targets and optimization of candidate compounds. In vivo rodent models, which recapitulate human metabolic disturbances, remain indispensable for evaluating preclinical efficacy and safety. Emerging evidence also underscores the potential of natural bioactive compounds as safer, multi-targeted therapeutic interventions. Future perspectives advocate the integration of advanced 3D tissue models, computational systems biology, and personalized medicine to improve translational relevance, reduce reliance on animal experimentation, and accelerate the development of next generation antiobesity therapeutics.