Horm Metab Res 2007; 39(10): 707-709
DOI: 10.1055/s-2007-985898
Review

© Georg Thieme Verlag KG Stuttgart · New York

Inflammation, Obesity, and the Metabolic Syndrome

J. S. Yudkin 1
  • 1University College London, Gower Street, London WC1E 6BT, UK
Further Information

Publication History

received 16.10.2006

accepted 18.1.2007

Publication Date:
22 October 2007 (online)

Abstract

Adipose tissue expresses cytokines which inhibit insulin signalling pathways. Obesity also results in impairment of endothelium-dependent vasodilatation to insulin. We have previously suggested that adipocytokines might contribute to the coexistence of insulin resistance and endothelial dysfunction. However, the adipocytokine best characterised as causing insulin resistance is tumour necrosis factor-α (TNF-α), a molecule which under normal circumstances circulates in low concentrations. We propose a vasoregulatory role for local deposits of fat around blood vessels, which may contribute both to insulin action and to vascular endothelial dysfunction. In particular, we propose that the localised fat depot around the origin of skeletal muscle arterioles may play a physiological role in blood flow distribution. Isolated rat arterioles 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 TNF-α from the fat surrounding the vessel origin - 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 periarteriolar fat and both periarterial and visceral fat, which may, through outside-to-inside signalling, play a direct role in producing the inflammatory changes found in atherosclerotic plaques, so explaining relationships between visceral fat, insulin resistance, and vascular disease.

References

Correspondence

Prof. J. S. Yudkin, MD, FRCP 

Emeritus Professor of Medicine

University College London

28, Huddleston Road

London

London N7 OAG

UK

Phone: +44/20/7607 38 55

Fax: +44/20/7607 25 06

Email: j.yudkin@ucl.ac.uk