TNF and obesity due to melanocortin 4 receptor deficiency: The number of macrophages can soar 40% within adipose tissue during obesity and it is positively associated with the aggravation of metabolic syndrome and the release of pro-inflammatory mediators such as IL-1β, IL-18, TNF-α, Nos2, and IL-6, which contribute to the development of insulin resistance and ultimately T2D (49, 102, 103).