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Free Fatty Acid Levels Modulate Microvascular Function

de Jongh, Renate T., Serné, Erik H., IJzerman, Richard G., de Vries, Greetje, Stehouwer, Coen D.A.·2004·Diabetes
DOI 10.2337/diabetes.53.11.2873
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Abstract

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 ∼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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Metadata

Authors
de Jongh, R. T., Serné, E. H., IJzerman, R. G., de Vries, G., & Stehouwer, C. D. A.
Affiliations
Department of Internal Medicine and Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, Amsterdam, the Netherlands
Venue
Diabetes
Publisher
American Diabetes Association
Published
2004-11-01
Volume
53
Issue
11
Pages
2873-2882
ISSN
  • 0012-1797
  • 1939-327X
DOI
10.2337/diabetes.53.11.2873
Cited by
179
References
11
Language
en

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