Obesity, blood vessels and metabolic syndrome

Obesity is rising worldwide at an alarming rate and so is the incidence of obesity-related disorders, such as the metabolic syndrome, type 2 diabetes and cardiovascular diseases. The obesity-dependent vascular damage appears to be derived from a variety of changes in the adipose tissue, leading to a chronic inflammatory state and dysregulation of adipocyte-derived factors. This, in turn, impairs vascular homeostasis by determining an unbalance between the protective effect of the nitric oxide pathway and the unfavourable action of the endothelin-1 system. In addition, hyperinsulinemia and insulin resistance contribute to vascular dysfunction because the opposing endothelium-dependent vasodilating and vasoconstrictor effects of insulin are shifted towards a predominant vasoconstriction in patients with obesity. Importantly, emerging evidence suggests that the vascular dysfunction of obesity is not only limited to the endothelium but also involves the other layers of the vessel wall. In particular, obesity-related changes in vascular smooth muscle seem to disrupt the physiological facilitatory action of insulin on the responsiveness to vasodilator stimuli, whereas the adventitia and the perivascular fat appear to be a source of proinflammatory and vasoactive factors that may contribute to endothelial and smooth muscle cell dysfunction and to the pathogenesis of vascular disease.