TNF and obesity due to melanocortin 4 receptor deficiency: It is well recognized that many major metabolic disorders, such as diabetes, results from obesity, which is associated with insulin resistance and a pro-inflammatory state.23 Expanded white adipose tissue (WAT) of obese subjects secretes many hormone (adipokine or adipocytokine), including sfrp5, leptin, adiponectin, TNF-α, resistin and IL-6, as critical players in regulating systemic lipid and glucose homeostasis as well as crosstalk between adipose tissue and other key metabolic organs, including the liver, muscle, and pancreas.