The impairment in endothelial function induced by non-esterified fatty acids can be reversed by insulin

Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called ‘insulin resistance syndrome’. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid^® (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80±4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid^® plus heparin increased the concentration of non-esterified fatty acids to 2.6±1.2 mmol/l and decreased EDV from 27.6±8.7 to 21.0±5.7 mlċmin^-1ċ100 ml^-1 tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4±9.5 mlċmin^-1ċ100 ml^-1 tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid^® plus heparin increased malondialdehyde levels from 0.67±0.22 to 1.2±0.37 μmol/l (P < 0.001), while hyperinsulinaemia did not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia.