Interplay mechanisms of action between vascular endothelial cells and perivascular adipose tissue in lean and obese subjects. In lean subjects, insulin and adiponectin stimulate endothelial cells to secrete nitric oxide and endothelin 1. This mechanism induces homeostasis between vasodilation and vasoconstriction, promotes glucose uptake and cytoprotection, and the oxidation of fatty acids in adipose tissue. Instead, in obese subjects, insulin resistance, the increased release of leptin and TNF-alpha stimulate vasoconstriction and reduction of NO bioavailability. Insulin resistance, Leptin, and TNF-alpha induce ROS production, the release of pro-inflammatory cytokines with inflammation, macrophage infiltration of PVAT and endothelial damage. Abbreviations: IR, insulin receptor; IRS, insulin receptor substrate; PI3K, phosphoinositide 3-kinase; Akt, protein kinase B; MAPK, mitogen-activated protein kinase; cGMP, cyclic guanosine monophosphate; AR, adiponectin receptor; LR, leptin receptor; TNF-a R, tumor necrosis factor-alpha receptor; NO, nitric oxide; eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; Prepro ET-1, Prepro endothelin-1; ET-a R, endothelin 1-a receptor; ET-b R, endothelin 1-b receptor; ROS, radical oxygen species; EC, endothelial cell; SMVC, smooth muscle vascular cell; PVAT, perivascular adipose tissue; TNF-a, tumor necrosis factor-alpha; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; NEFA, non-esterified fatty acids.