In rat [147] and rabbit [148] models of diet-induced obesity and surgically induced OA, an increase in pro-inflammatory macrophages and inflammatory mediators such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF) has been observed within the synovium, contributing to the progression of OA [148]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.