In addition, beyond the above mentioned alterations, HFD animals displayed a chronic low-grade systemic inflammation and immune system activation (e.g., a meta-inflammatory condition), characterized by a marked increase in pro-inflammatory cytokines (e.g., TNF, IL-1β and IL-6), which seem to be relevantly involved in the pathogenesis of obesity-related insulin resistance [26–29]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.