CREB1 and obesity due to melanocortin 4 receptor deficiency: 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.