Background: Adipose tissue expansion in obesity is accompanied by extracellular matrix (ECM) remodelling, regulated by matrix metalloproteinases (MMPs). Visceral adipose tissue (VAT) is metabolically more active than subcutaneous adipose tissue (SAT). However, depot-specific differences in proteolytic activity and protein glycooxi-dation remain incompletely characterized. Methods: In this case-control study, we assessed the activity of six matrix metallo-proteinases (MMP-1, -2, -7, -9, -11, -13) using a fluorescence resonance energy transfer (FRET) assay and quantified advanced glycation and glycooxidation-related markers in paired VAT, SAT and plasma samples obtained from 40 patients with obesity and 21 non-obese controls. Results: The activities of all assessed MMPs were greater in patients with obesity than in the control group (p < 0.01 for all MMPs). Direct tissue-compartment comparisons showed that MMP activity and glycooxidation-related markers were most pronounced in VAT, with markedly higher values in obese individuals compared with controls. In VAT of obese individuals, median MMP activity was approximately 50–60% higher compared with controls. Amyloid cross-β-structure, vesperlysine and pentosidine were significantly elevated in VAT in obesity, whereas plasma levels were markedly lower and showed limited group differences. No significant differences were observed between obese par-ticipants with and without metabolic syndrome. Conclusions: Obesity is associated with a depot-specific molecular profile charac-terized by enhanced proteolytic and glycooxidative activity predominantly within vis-ceral adipose tissue. These findings highlight the importance of tissue-compartment–specific assessment in obesity.

Adipose tissue expansion in obesity is accompanied by extracellular matrix (ECM) remodeling, regulated by matrix metalloproteinases (MMPs). Visceral adipose tissue (VAT) is metabolically more active than subcutaneous adipose tissue (SAT). However, depot-specific differences in proteolytic activity and protein glycooxidation remain incompletely characterized. In this case–control study, we assessed the activity of six matrix metalloproteinases (MMP-1, -2, -7, -9, -11, and -13) using a fluorescence resonance energy transfer (FRET) assay and quantified advanced glycation- and glycooxidation-related markers in paired VAT, SAT, and plasma samples obtained from 40 patients with obesity and 21 non-obese controls. The activities of all assessed MMPs were greater in patients with obesity than in the control group (p < 0.01 for all MMPs). Direct tissue-compartment comparisons showed that MMP activity and glycooxidation-related markers were most pronounced in VAT, with markedly higher values in obese individuals compared with controls. In VAT of obese individuals, median MMP activity was approximately 50–60% higher compared with controls. Amyloid cross-β-structure, vesperlysine, and pentosidine were significantly elevated in VAT in obesity, whereas plasma levels were markedly lower and showed limited group differences. No significant differences were observed between obese participants with and without metabolic syndrome. Obesity is associated with a depot-specific molecular profile characterized by enhanced proteolytic and glycooxidative activity predominantly within visceral adipose tissue. These findings highlight the importance of tissue-compartment-specific assessment in obesity.

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.