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Adipose tissue expresses cytokines that inhibit insulin signalling pathways in liver and muscle. Obesity also results in impairment of endothelium-dependent vasodilatation in response 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 NO synthesis is impaired, resulting in unopposed vasoconstriction. We propose that this vasoconstriction is the consequence of production of the adipocytokine tumour necrosis factor _ 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 relations between visceral fat, insulin resistance, and vascular disease.
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J. Vasc. Biol. 42, Sup:2 (2005) p23