LEP and obesity due to melanocortin 4 receptor deficiency: With onset of OA there is a switch from adipokine synthesis to receptor synthesis (Francin et al., 2011). Leptin itself enhances production of catabolic MMP enzymes in OA cartilage (Iliopoulos et al., 2007; Koskinen et al., 2011). It is believed that leptin may mediate the pro-OA effects of obesity rather than simply the increased load observed in weight baring joints