Early studies have indicated that systemic inflammation associated with obesity and high-fat diets (HFDs) in obese humans and HFD-fed rats results in higher levels of circulating pro-inflammatory cytokines (IL-1, IL-6, and TNF-α) and increased macrophage infiltration into the WAT when compared to the controls [47]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.