TY - JOUR
T1 - "Vasocrine" signalling from perivascular fat
T2 - A mechanism linking insulin resistance to vascular disease
AU - Yudkin, John S.
AU - Eringa, Etto
AU - Stehouwer, Coen D.A.
PY - 2005/5/21
Y1 - 2005/5/21
N2 - 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 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 relations between visceral fat, insulin resistance, and vascular disease.
AB - 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 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 relations between visceral fat, insulin resistance, and vascular disease.
UR - http://www.scopus.com/inward/record.url?scp=19744362790&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S0140-6736(05)66585-3
DO - https://doi.org/10.1016/S0140-6736(05)66585-3
M3 - Comment/Letter to the editor
C2 - 15910955
SN - 0140-6736
VL - 365
SP - 1817
EP - 1820
JO - Lancet
JF - Lancet
IS - 9473
ER -