PVAT also controls insulin-induced vasoreactivity in the muscle microcirculation through secretion of adiponectin and subsequent AMPKα2 signaling (with resultant eNOS activation and NO production) but obesity-related PVAT inhibits insulin-induced vasodilation, which can be restored by inhibition of the inflammatory kinase JNK in PVAT [103]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.