Abstract / Summary
Obesity has reached epidemic proportions worldwide, affecting approximately 890 million adults as of 2022, and projections indicate the number will exceed 1.5 billion by 2035. While excess body weight is frequently framed as a simple imbalance between caloric intake and expenditure, the pathophysiology of obesity is considerably more complex, involving adipose tissue dysfunction, chronic low-grade inflammation, disrupted adipokine secretion, and progressive insulin resistance. This narrative-analytical review synthesizes current evidence on the molecular and systemic mechanisms through which dysfunctional adipose tissue, particularly visceral fat, drives cardiometabolic disease. The review examines adipocyte hypertrophy and extracellular matrix remodeling, ectopic lipid deposition, leptin and adiponectin dysregulation, macrophage polarization and inflammatory signaling through NF-kB, JNK, and the NLRP3 inflammasome, mitochondrial dysfunction, and the emerging phenotype of sarcopenic obesity. Synthesizing data from systematic reviews, prospective cohort studies, and clinical metabolic research published between 2020 and 2026, the review proposes an integrated clinical framework that moves beyond body weight as a primary treatment target toward metabolic health, tissue composition, and functional outcomes. Findings are relevant to internists, endocrinologists, cardiologists, and preventive medicine practitioners.