NOS3 and obesity due to melanocortin 4 receptor deficiency: In obesity, chemerin from PVAT contributes to the positive amplification of sympathetic nerve stimulation and thereby increases vascular tone [119], while chemerin in the vessel wall decreases the expression of the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis, GTP cyclohydrolase I (GTPCH1), decreases eNOS activation and NO production, and promotes ROS generation [120,121].