Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy

R.T. de Jongh, E.H. Serné, R.G. Ijzerman, G. de Vries, C.D.A. Stehouwer

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Abstract

Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy.

de Jongh RT, Serne EH, Ijzerman RG, de Vries G, Stehouwer CD.

Department of Internal Medicine, Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.

To test the hypothesis that free fatty acids (FFAs) modulate microvascular function and that this contributes to obesity-associated insulin resistance, hypertension, and microangiopathy, we examined the effects of both FFA elevation in lean women and FFA lowering in obese women on skin microvascular function. A total of 16 lean and 12 obese women underwent, respectively, Intralipid plus heparin (or saline) infusion and overnight acipimox (or placebo) treatment. We measured capillary recruitment with capillaroscopy and endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside before and during hyperinsulinemia (40 mU . m(-2) . min(-1)). FFA elevation impaired capillary recruitment and acetylcholine-mediated vasodilation before (44.6 +/- 16.8 vs. 56.9 +/- 18.9%, P < 0.05; and 338 +/- 131 vs. 557 +/- 162%, P < 0.01, respectively) and during (54.0 +/- 21.3 vs. 72.4 +/- 25.4%, P < 0.01; and 264 +/- 186 vs. 685 +/- 199%, P < 0.01, respectively) hyperinsulinemia. FFA lowering improved capillary recruitment before (50.9 +/- 14.6 vs. 37.4 +/- 9.3%, P < 0.01) and during (66.8 +/- 20.6 vs. 54.8 +/- 15.4%, P < 0.05) hyperinsulinemia. Changes in FFA levels were inversely associated with changes in capillary recruitment and insulin sensitivity in lean (r = -0.46, P = 0.08; and r = -0.56, P = 0.03) and in obese (r = -0.70, P = 0.02; and r = -0.62, P = 0.04) women. Regression analyses showed that changes in capillary recruitment statistically explained approximately 29% of the association between changes in FFA levels and insulin sensitivity. In conclusion, FFA levels modulate microvascular function and may contribute to obesity-associated insulin resistance, hypertension, and microangiopathy
Original languageEnglish
Pages (from-to)2873-2882
JournalDiabetes
Volume53
Issue number11
DOIs
Publication statusPublished - 1 Jan 2004

Cite this

@article{242531a008e14c4a95864e39eed8b010,
title = "Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy",
abstract = "Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy.de Jongh RT, Serne EH, Ijzerman RG, de Vries G, Stehouwer CD.Department of Internal Medicine, Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.To test the hypothesis that free fatty acids (FFAs) modulate microvascular function and that this contributes to obesity-associated insulin resistance, hypertension, and microangiopathy, we examined the effects of both FFA elevation in lean women and FFA lowering in obese women on skin microvascular function. A total of 16 lean and 12 obese women underwent, respectively, Intralipid plus heparin (or saline) infusion and overnight acipimox (or placebo) treatment. We measured capillary recruitment with capillaroscopy and endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside before and during hyperinsulinemia (40 mU . m(-2) . min(-1)). FFA elevation impaired capillary recruitment and acetylcholine-mediated vasodilation before (44.6 +/- 16.8 vs. 56.9 +/- 18.9{\%}, P < 0.05; and 338 +/- 131 vs. 557 +/- 162{\%}, P < 0.01, respectively) and during (54.0 +/- 21.3 vs. 72.4 +/- 25.4{\%}, P < 0.01; and 264 +/- 186 vs. 685 +/- 199{\%}, P < 0.01, respectively) hyperinsulinemia. FFA lowering improved capillary recruitment before (50.9 +/- 14.6 vs. 37.4 +/- 9.3{\%}, P < 0.01) and during (66.8 +/- 20.6 vs. 54.8 +/- 15.4{\%}, P < 0.05) hyperinsulinemia. Changes in FFA levels were inversely associated with changes in capillary recruitment and insulin sensitivity in lean (r = -0.46, P = 0.08; and r = -0.56, P = 0.03) and in obese (r = -0.70, P = 0.02; and r = -0.62, P = 0.04) women. Regression analyses showed that changes in capillary recruitment statistically explained approximately 29{\%} of the association between changes in FFA levels and insulin sensitivity. In conclusion, FFA levels modulate microvascular function and may contribute to obesity-associated insulin resistance, hypertension, and microangiopathy",
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doi = "10.2337/diabetes.53.11.2873",
language = "English",
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Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy. / de Jongh, R.T.; Serné, E.H.; Ijzerman, R.G.; de Vries, G.; Stehouwer, C.D.A.

In: Diabetes, Vol. 53, No. 11, 01.01.2004, p. 2873-2882.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy

AU - de Jongh, R.T.

AU - Serné, E.H.

AU - Ijzerman, R.G.

AU - de Vries, G.

AU - Stehouwer, C.D.A.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy.de Jongh RT, Serne EH, Ijzerman RG, de Vries G, Stehouwer CD.Department of Internal Medicine, Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.To test the hypothesis that free fatty acids (FFAs) modulate microvascular function and that this contributes to obesity-associated insulin resistance, hypertension, and microangiopathy, we examined the effects of both FFA elevation in lean women and FFA lowering in obese women on skin microvascular function. A total of 16 lean and 12 obese women underwent, respectively, Intralipid plus heparin (or saline) infusion and overnight acipimox (or placebo) treatment. We measured capillary recruitment with capillaroscopy and endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside before and during hyperinsulinemia (40 mU . m(-2) . min(-1)). FFA elevation impaired capillary recruitment and acetylcholine-mediated vasodilation before (44.6 +/- 16.8 vs. 56.9 +/- 18.9%, P < 0.05; and 338 +/- 131 vs. 557 +/- 162%, P < 0.01, respectively) and during (54.0 +/- 21.3 vs. 72.4 +/- 25.4%, P < 0.01; and 264 +/- 186 vs. 685 +/- 199%, P < 0.01, respectively) hyperinsulinemia. FFA lowering improved capillary recruitment before (50.9 +/- 14.6 vs. 37.4 +/- 9.3%, P < 0.01) and during (66.8 +/- 20.6 vs. 54.8 +/- 15.4%, P < 0.05) hyperinsulinemia. Changes in FFA levels were inversely associated with changes in capillary recruitment and insulin sensitivity in lean (r = -0.46, P = 0.08; and r = -0.56, P = 0.03) and in obese (r = -0.70, P = 0.02; and r = -0.62, P = 0.04) women. Regression analyses showed that changes in capillary recruitment statistically explained approximately 29% of the association between changes in FFA levels and insulin sensitivity. In conclusion, FFA levels modulate microvascular function and may contribute to obesity-associated insulin resistance, hypertension, and microangiopathy

AB - Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy.de Jongh RT, Serne EH, Ijzerman RG, de Vries G, Stehouwer CD.Department of Internal Medicine, Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.To test the hypothesis that free fatty acids (FFAs) modulate microvascular function and that this contributes to obesity-associated insulin resistance, hypertension, and microangiopathy, we examined the effects of both FFA elevation in lean women and FFA lowering in obese women on skin microvascular function. A total of 16 lean and 12 obese women underwent, respectively, Intralipid plus heparin (or saline) infusion and overnight acipimox (or placebo) treatment. We measured capillary recruitment with capillaroscopy and endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside before and during hyperinsulinemia (40 mU . m(-2) . min(-1)). FFA elevation impaired capillary recruitment and acetylcholine-mediated vasodilation before (44.6 +/- 16.8 vs. 56.9 +/- 18.9%, P < 0.05; and 338 +/- 131 vs. 557 +/- 162%, P < 0.01, respectively) and during (54.0 +/- 21.3 vs. 72.4 +/- 25.4%, P < 0.01; and 264 +/- 186 vs. 685 +/- 199%, P < 0.01, respectively) hyperinsulinemia. FFA lowering improved capillary recruitment before (50.9 +/- 14.6 vs. 37.4 +/- 9.3%, P < 0.01) and during (66.8 +/- 20.6 vs. 54.8 +/- 15.4%, P < 0.05) hyperinsulinemia. Changes in FFA levels were inversely associated with changes in capillary recruitment and insulin sensitivity in lean (r = -0.46, P = 0.08; and r = -0.56, P = 0.03) and in obese (r = -0.70, P = 0.02; and r = -0.62, P = 0.04) women. Regression analyses showed that changes in capillary recruitment statistically explained approximately 29% of the association between changes in FFA levels and insulin sensitivity. In conclusion, FFA levels modulate microvascular function and may contribute to obesity-associated insulin resistance, hypertension, and microangiopathy

U2 - 10.2337/diabetes.53.11.2873

DO - 10.2337/diabetes.53.11.2873

M3 - Article

VL - 53

SP - 2873

EP - 2882

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -