Obesity as a Multifactorial Chronic Disease: Molecular Mechanisms, Systemic Impact, and Emerging Digital...

Obesity is a multifactorial chronic disease resulting from complex genetic, molecular, environmental, and behavioral interactions. Its prevalence rises worldwide, affecting cardiovascular, metabolic, oncological, hepatic, respiratory, and skeletal health. Beyond caloric excess, genetic predisposition, epigenetic modifications, gut microbiota dysbiosis, endocrine-disrupting agents, circadian misalignment, and intergenerational and prenatal influences are critical determinants of obesity risk. Core pathophysiological mechanisms include insulin resistance, dyslipidemia, chronic low-grade inflammation, and neuroendocrine dysregulation of appetite and energy balance. These processes are linked to comorbidities such as type 2 diabetes, hypertension, atherosclerosis, fatty liver disease, sleep apnea, osteoporosis, and cancer. Advances in molecular profiling, metabolic phenotyping, and body composition analysis are refining obesity classification and enabling precise risk stratification. Current therapeutic strategies include behavioral interventions addressing stress-related mechanisms, pharmacological therapies such as GLP-1 receptor agonists, emerging gene therapy approaches, and bariatric surgery. Gut-derived hormones (leptin, ghrelin, GLP-1, PYY, CCK) are recognized as pivotal regulators of appetite and weight. Preventive strategies increasingly emphasize circadian alignment, while epigenetic inheritance and prenatal exposures such as maternal obesity or smoking highlight early-life programming in future metabolic health. Additionally, artificial intelligence-based platforms and personalized nutrition provide innovative opportunities for individualized prevention and management. This review synthesizes contemporary evidence on the biological basis, systemic consequences, preventive strategies, and evolving therapeutic modalities of obesity, affirming its recognition as a complex chronic disease requiring personalized, multidisciplinary care.