INS and obesity due to melanocortin 4 receptor deficiency: These findings, in addition to the observations that local accumulation of adipose tissue is consistently related to decreased flow-mediated vasodilation (Albu et al., 2005), fasting insulin levels and insulin resistance in humans (Rittig et al., 2008), support the involvement PVAT-derived factors as paracrine, rather than endocrine mediators of both microvascular dysfunction and insulin resistance in obesity.