Impaired arterial vasorelaxation, due primarily to endothelial dysfunction, is associated with obesity. To clarify the relationship with insulin resistance and other metabolic disturbances, we studied endothelial-dependent and -independent vascular responses in rats with dietary-induced obesity. Dietary-obese rats had significantly higher body weights (10-32%; P < 0.001) and fat-pad masses (220-280%; P < 0.001) than lean controls, together with raised plasma levels of triacylglycerols (15-80%; P < 0.001), non-esterified fatty acids (13-38%; P < 0.05) and leptin (85-180%; P < 0.001). However, measures of insulin sensitivity (including the hyperinsulinaemic-euglycaemic clamp in a parallel experiment) were comparable with those in controls. Contractions induced in mesenteric arteries by noradrenaline (0.5-8μmol/l) were comparable in lean and obese groups, but vasorelaxation in noradrenaline-preconstricted arteries was markedly reduced in dietary-obese rats of both sexes. Concentration-response curves to endothelium-dependent vasorelaxants (acetylcholine, A23187 and insulin) showed significant reductions in maximal relaxation (20-95% less than in leans; P < 0.001) and significant rightward shifts in EC40 (concentration giving 40% of maximal response) (P < 0.01). Relaxation in response to the direct NO donor, sodium nitroprusside, showed a lesser impairment (12%; P < 0.01) in dietary-obese rats. Maximal relaxation to acetylcholine was correlated inversely in both sexes with fat-pad mass (r2 = 0.37, P < 0.05) and plasma triacylglycerols (r2 = 0.51, P < 0.01), and with leptin in males only (r2 = 0.35, P < 0.05). Independent determinants of acetylcholine-induced relaxation were fat mass and plasma triacylglycerols; plasma insulin and insulin sensitivity had no effect. Dietary-induced obesity severely impaired arterial relaxation in both sexes, particularly at the endothelial level. This is not attributable to insulin resistance, but may be related to moderate hypertriglyceridaemia.
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Research Article|
October 01 2001
Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols
Ebrahim K. NADERALI;
*Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, UCD, Daulby Street, Liverpool L69 3GA, U.K.
Correspondence: Dr E. K. Naderali (e-mail [email protected]).
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Michael J. BROWN;
Michael J. BROWN
*Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, UCD, Daulby Street, Liverpool L69 3GA, U.K.
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Lucy C. PICKAVANCE;
Lucy C. PICKAVANCE
*Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, UCD, Daulby Street, Liverpool L69 3GA, U.K.
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John P.H. WILDING;
John P.H. WILDING
*Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, UCD, Daulby Street, Liverpool L69 3GA, U.K.
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Patrick J. DOYLE;
Patrick J. DOYLE
†Novo-Nordisk A/S, Brudelysvej 28, 2880 Bagsvaerd, Denmark
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Gareth WILLIAMS
Gareth WILLIAMS
*Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, UCD, Daulby Street, Liverpool L69 3GA, U.K.
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Publisher: Portland Press Ltd
Received:
March 13 2001
Revision Received:
May 23 2001
Accepted:
July 09 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 101 (5): 499–506.
Article history
Received:
March 13 2001
Revision Received:
May 23 2001
Accepted:
July 09 2001
Citation
Ebrahim K. NADERALI, Michael J. BROWN, Lucy C. PICKAVANCE, John P.H. WILDING, Patrick J. DOYLE, Gareth WILLIAMS; Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols. Clin Sci (Lond) 1 November 2001; 101 (5): 499–506. doi: https://doi.org/10.1042/cs1010499
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