Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: Effects of fat composition and gender

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Open Access funded by Biotechnology and Biological Sciences Research Council under a Creative Commons license
Background and aims We have reported that adverse effects on flow-mediated dilation of an acute elevation of non-esterified fatty acids rich in saturated fat (SFA) are reversed following addition of long-chain (LC) n-3 polyunsaturated fatty acids (PUFA), and hypothesised that these effects may be mediated through alterations in insulin signalling pathways. In a subgroup, we explored the effects of raised NEFA enriched with SFA, with or without LC n-3 PUFA, on whole body insulin sensitivity (SI) and responsiveness of the endothelium to insulin infusion. Methods and results Thirty adults (mean age 27.8 y, BMI 23.2 kg/m2) consumed oral fat loads on separate occasions with continuous heparin infusion to elevate NEFA between 60 and 390 min. For the final 150 min, a hyperinsulinaemic-euglycaemic clamp was performed, whilst FMD and circulating markers of endothelial function were measured at baseline, pre-clamp (240 min) and post-clamp (390 min). NEFA elevation during the SFA-rich drinks was associated with impaired FMD (P = 0.027) whilst SFA + LC n-3 PUFA improved FMD at 240 min (P = 0.003). In males, insulin infusion attenuated the increase in FMD with SFA + LC n-3 PUFA (P = 0.049), with SI 10% greater with SFA + LC n-3 PUFA than SFA (P = 0.041). Conclusion This study provides evidence that NEFA composition during acute elevation influences both FMD and SI, with some indication of a difference by gender. However our findings are not consistent with the hypothesis that the effects of fatty acids on endothelial function and SI operate through a common pathway. This trial was registered at clinical trials.gov as NCT01351324 on 6th May 2011.
Fatty acids, Flow-mediated dilatation, Hyperinsulinaemic-euglycaemic clamp, Insulin signalling, Nitric oxide, Adult, Biomarkers, Blood Glucose, Brachial Artery, Cross-Over Studies, Endothelium, Vascular, England, Fatty Acids, Nonesterified, Fatty Acids, Omega-3, Female, Glucose Clamp Technique, Humans, Insulin, Insulin Resistance, Male, Single-Blind Method, Time Factors, Ultrasonography, Up-Regulation, Vasodilation
Nutr Metab Cardiovasc Dis, 2015, 25 (6), pp. 575 - 581