Microvascular endothelial dysfunction in human obesity: role of TNF-α

CONTEXT: Endothelium guarantees the vascular homeostasis by the opposite action of substances with vasodilating/anti-thrombogenic and vasoconstricting/prothrombotic activities. Obesity is characterized by endothelial dysfunction associated with a condition of vascular low-grade inflammation. EVIDENCE ACQUISITION: Analysis of available basic or clinical papers published in peer-reviewed international journals on microcirculation and obesity. EVIDENCE SYNTHESIS: Vascular low-grade inflammation which characterizes obesity is secondary to abnormal production of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF-α). TNF-α, generated either in small vessels or within the perivascular adipose tissue (PVAT) of obese patients, stimulates the reactive oxygen species generation, mainly through NAD(P)H oxidase activation, which in turn reduces nitric oxide (NO) availability. These aspects are lighted by the insulin resistance status and macronutrient intake which characterize the obesity condition. Oxidant excess has also been proposed as a mechanism whereby TNF-α interferes with the Endothelin-1/NO system at the level of small vessels from obese patients. CONCLUSIONS: In obesity, microvasculature from visceral fat is an important source of low-grade inflammation and oxidative stress that, together with the PVAT, directly contribute to vascular changes, favouring the development and acceleration of the vascular atherothrombotic process in this clinical condition.