Key result
Obesity is linked to loss of perivascular fat anticontractile function and ~85% higher TNFR1 expression.
Why the study?
The local mechanisms by which inflammation in adipose tissue causes vascular dysfunction are unknown.
Observational
Adiponectin secreted by perivascular adipose tissue modulates local vascular tone by increasing nitric oxide bioavailability, a protective mechanism lost in obesity due to adipocyte hypertrophy, hypoxia, and inflammation.
Does not change clinical management; leaves open whether targeting perivascular fat inflammation benefits obese patients.
BACKGROUND: Inflammation in adipose tissue has been implicated in vascular dysfunction, but the local mechanisms by which this occurs are unknown. METHODS AND RESULTS: Small arteries with and without perivascular adipose tissue were taken from subcutaneous gluteal fat biopsy samples and studied with wire myography and immunohistochemistry. We established that healthy adipose tissue around human small arteries secretes factors that influence vasodilation by increasing nitric oxide bioavailability. However, in perivascular fat from obese subjects with metabolic syndrome (waist circumference 111+/-2.8 versus 91.1+/-3.5 cm in control subjects, P<0.001; insulin sensitivity 41+/-5.9% versus 121+/-18.6% in control subjects, P<0.001), the loss of this dilator effect was accompanied by an increase in adipocyte area (1786+/-346 versus 673+/-60 mum(2), P<0.01) and immunohistochemical evidence of inflammation (tumor necrosis factor receptor 1 12.4+/-1.1% versus 6.7+/-1%, P<0.001). Application of the cytokines tumor necrosis factor receptor-alpha and interleukin-6 to perivascular fat around healthy blood vessels reduced dilator activity, resulting in the obese phenotype. These effects could be reversed with free radical scavengers or cytokine antagonists. Similarly, induction of hypoxia stimulated inflammation and resulted in loss of anticontractile capacity, which could be rescued by catalase and superoxide dismutase or cytokine antagonists. Incubation with a soluble fragment of adiponectin type 1 receptor or inhibition of nitric oxide synthase blocked the vasodilator effect of healthy perivascular adipose tissue. CONCLUSIONS: We conclude that adipocytes secrete adiponectin and provide the first functional evidence that it is a physiological modulator of local vascular tone by increasing nitric oxide bioavailability. This capacity is lost in obesity by the development of adipocyte hypertrophy, leading to hypoxia, inflammation, and oxidative stress.
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Greenstein et al. (2009) conducted an observational in Obesity with metabolic syndrome. Obesity with metabolic syndrome vs. Healthy control subjects was evaluated on Tumor necrosis factor receptor 1 expression (inflammation) (p=<0.001). Perivascular fat from obese patients lost its normal anticontractile capacity due to adipocyte hypertrophy, hypoxia, and inflammation, including increased tumor necrosis factor receptor 1 (12.4% vs 6.7%; P<0.001).
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