Yudkin, John S.; Eringa, E.; Stehouwer, Coen D.A.; (2005) Hypothesis: ‘Vasocrine’ signalling from perivascular fat - a mechanism linking insulin resistance and vascular disease. The Lancet , 365 (9473) pp. 1817-1820. 10.1016/S0140-6736(05)66585-3.

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Abstract

Adipose tissue expresses cytokines which inhibit insulin signalling pathways in liver and muscle. Obesity also results in impairment of endothelium-dependent vasodilatation to insulin. We propose a vasoregulatory role for local deposits of fat around the origin of arterioles supplying skeletal muscle. Isolated first order arterioles from rat cremaster muscle are under dual regulation by insulin, which activates both endothelin-1 mediated vasoconstriction and nitric oxide mediated vasodilatation. In obese rat arterioles, insulin-stimulated nitric oxide synthesis is impaired, resulting in unopposed vasoconstriction. We propose this to be the consequence of production of the adipocytokine tumour necrosis factor-α from the cuff of fat seen surrounding the origin of the arteriole in obese rats – a depot to which we ascribe a specialist vasoregulatory role. We suggest that this cytokine accesses the nutritive vascular tree to inhibit insulin-mediated capillary recruitment – a mechanism we term ‘vasocrine’ signalling. We also suggest a homology between this vasoactive periarteriolar fat and both periarterial and visceral fat, which may explain relationships between visceral fat, insulin resistance and vascular disease.

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