It is worth noting that Griffin et al. proved that a lack of leptin does not lead to an increase in the incidence of spontaneous OA in a mouse model, although its body weight is extremely high, indicating that the loss of leptin signaling may protect the human body from the progress of OA [4], which has drawn our attention whether leptin plays an initial role in the pathogenesis of obesity-related OA or it is just a driver of OA progress, and by what mechanism does leptin promote OA. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.