TNF and obesity due to melanocortin 4 receptor deficiency: In mechanism, TNF-α and IL-1β were found to promote catabolism and inhibit anabolism of extracellular matrix of the disc.60,63 Besides, TNF-α and IL-1β could also promote some pro-inflammatory mediator expressions in NP, including IL-6, IL-8, IL-17, iNOS, etc.60 These findings suggested that obesity related pro-inflammatory cytokines might serve as critical links between obesity and IDD (Fig. 1).