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Free Fatty Acid Levels Modulate Microvascular Function

Relevance for Obesity-Associated Insulin Resistance, Hypertension, and Microangiopathy

¹ Department of Internal Medicine and Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, Amsterdam, the Netherlands
² Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Hospital, Maastricht, 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 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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