Free Fatty Acid Levels Modulate Microvascular Function: Relevance for Obesity-Associated Insulin Resistance, Hypertension, and Microangiopathy

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 P P P P P 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.