• Metabolic syndrome (obesity, diabetes, dyslipidemia) is an independent risk factor for osteoarthritis, with each 1 kg/m2 increase in BMI raising knee OA risk by 15%.
• Adipokine imbalance (leptin up 3.2-fold, adiponectin down 40%) drives cartilage degradation via MMP-13 activation and TIMP-2 inhibition.
• Osteoarthritic chondrocytes exhibit metabolic reprogramming: enhanced glycolysis, mitochondrial dysfunction, and lipid accumulation (free fatty acids up 1.8-fold).
• A metabolic-inflammatory feedback loop (adipose-derived IL-1β/TNF-α activating NF-κB) exacerbates OA, suggesting potential for metabolic-targeted therapies.