Restoring perivascular adipose tissue function in obesity using exercise

Sophie Saxton, Lauren Toms, Robert G Aldous, Sarah Withers, Jacqueline Ohanian, Anthony Heagerty

Research output: Contribution to journalArticlepeer-review


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 hyperinsulinemia, 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 or pharmacological intervention at the level of nitric oxide signalling, will restore function and treat the vascular complications of obesity.
Original languageEnglish
JournalCardiovascular Drugs and Therapy
Publication statusAccepted/In press - 21 Dec 2020


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