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. Here, RETN is linked to obesity due to melanocortin 4 receptor deficiency.