Restoring Perivascular Adipose Tissue Function in Obesity Using Exercise

Purpose

Perivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating vascular tone. This effect is mediated via sympathetic nervous stimulation of PVAT by a mechanism which involves noradrenaline uptake through organic cation transporter 3 (OCT3) and β₃-adrenoceptor-mediated adiponectin release. In obesity, autonomic dysfunction occurs, which may result in a loss of PVAT function and subsequent vascular disease. Accordingly, we have investigated abnormalities in obese PVAT, and the potential for exercise in restoring function.

Methods

Vascular contractility to electrical field stimulation (EFS) was assessed ex vivo in the presence of pharmacological tools in ±PVAT vessels from obese and exercised obese mice. Immunohistochemistry was used to detect changes in expression of β₃-adrenoceptors, OCT3 and tumour necrosis factor-α (TNFα) in PVAT.

Results

High fat feeding induced hypertension, hyperglycaemia, and hyperinsulinaemia, which was reversed using exercise, independent of weight loss. Obesity induced a loss of the PVAT anti-contractile effect, which could not be restored via β₃-adrenoceptor activation. Moreover, adiponectin no longer exerts vasodilation. Additionally, exercise reversed PVAT dysfunction in obesity by reducing inflammation of PVAT and increasing β₃-adrenoceptor and OCT3 expression, which were downregulated in obesity. Furthermore, the vasodilator effects of adiponectin were restored.

Conclusion

Loss of neutrally mediated PVAT anti-contractile function in obesity will contribute to the development of hypertension and type II diabetes. Exercise training will restore function and treat the vascular complications of obesity.

     

Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors

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Current fluconazole treatment regimens result in under-dosing of critically ill adults during early therapy

European Journal of Clinical Microbiology & Infectious Diseases - To evaluate current fluconazole treatment regimens in critically ill adults over the typical treatment course. Data from...