Obesity as a Disease of Visceral Adipose Tissue: MMP Activation and AGE Accumulation as Key Mechanisms of Metabolic Complications

Obesity is increasingly recognized as a chronic molecular disease of visceral adipose tissue rather than a simple excess of body weight. Structural remodeling and biochemical damage within adipose depots — particularly extracellular matrix (ECM) degradation and oxidative protein modification — are believed to play a central role in the development of metabolic complications. This study evaluated matrix metalloproteinase (MMP) activity and protein glycooxidation in visceral and subcutaneous adipose tissue, as well as plasma in individuals with obesity. Using a fluorescence resonance energy transfer (FRET)–based assay and fluorimetric quantification of advanced glycation end-products (AGEs), we demonstrated markedly increased activity of all analyzed MMPs (MMP-1, -2, -7, -9, -11, -13) and significantly higher accumulation of selected AGE-related structures (dityrosine (DT), amyloid cross-β-structure, vesperlysine (VES) , pentosidine (PEN)) in visceral adipose tissue of obese patients. These findings indicate that visceral adipose tissue forms a localized inflammatory–proteolytic microenvironment rather than a reflection of systemic circulating pathology. The coexistence of ECM degradation and glycooxidation may mechanistically promote insulin resistance and cardiometabolic risk. These findings suggest that clinical assessment of obesity may require more than anthropometric parameters and circulating biomarkers. Molecular profiling of visceral adipose tissue — directly or via future non-invasive surrogate markers — could improve patient stratification, support personalized metabolic risk prediction and optimize therapeutic decision-making.