However, leptin may also contribute to cartilage destruction through a systemic effect, as suggested by our previous study, negatively associating serum leptin levels with knee cartilage volume [14], and as well as studies showing that BMI was associated with leptin concentrations in synovial fluid [16], and that leptin-deficient mice were less likely to have obesity-induced cartilage degeneration [41]. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.