title: "Vasocrine" signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease.
abstract: 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 alpha 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.
authors.affiliation: Diabetes and Cardiovascular Disease Academic Unit, Department of Medicine, Royal Free and University College Medical School, The Archway Campus, Holborn Union Building, 2-10 Highgate Hill, London N19 5LW, UK. j.yudkin@ucl.ac.uk
authors.forename: John S
authors.initials: JS
authors.lastname: Yudkin
authors.forename: Etto
authors.initials: E
authors.lastname: Eringa
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000503:physiopathology; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology*
chemical_list: D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase