LEP and obesity due to melanocortin 4 receptor deficiency: Leptin concentration in synovial fluid is increased and the intra-articular negative regulators of leptin sOb-R (soluble leptin receptor) and SOCS-3 (suppressor of cytokine signaling-3) are diminished in obesity, leading to increased stimulation by leptin of matrix MMP-1, MMP-3, IL-6 and NO production by chondrocytes [53].