Notably, the ANGPTL2 promoter harbors a CREB binding site[55] and is gradually upregulated during adipocyte differentiation.[13, 53] Thus, is likely that CREB directly upregulates ANGPTL2 expression during adipocyte differentiation, meaning that the feedback loop enhances ANGPTL2 and CD146 expression, which increases obesity and inflammation. Here, ANGPTL2 is linked to obesity due to melanocortin 4 receptor deficiency.