L. Lind et al., The impairment in endothelial function induced by non-esterified fatty acids can be reversed by insulin, CLIN SCI, 99(3), 2000, pp. 169-174
Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerid
es) and non-esterified (free) fatty acids, and hyperinsulinaemia are often
found in the same subjects, the so-called 'insulin resistance syndrome'. Th
e present study aims to investigate how elevated levels of non-esterified f
atty acids, hyperinsulinaemia and the combination of these factors affects
endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on
two occasions. lntralipid(R) (plus heparin) or saline (0.9% NaCl) was infu
sed 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 dete
rmined by measuring plasma malondialdehyde levels. Infusion of Intralipid(R
) 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 ml.
min(-1).100 ml(-1) tissue (P < 0.01). This effect was completely reversed b
y hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 3
0.4 +/- 9.5 ml.min(-1).100 ml(-1) tissue; P < 0.01), while endothelium-inde
pendent vasodilatation was unaltered by the interventions. infusion of Intr
alipid(R) plus heparin increased malondialdehyde levels from 0.67 +/- 0.22
to 1.2 +/- 0.37 mu mol/l (P < 0.001), while hyperinsulinaemia did not chang
e the malondialdehyde level. In conclusion, an acute increase in serum leve
ls of nonesterified fatty acids increased lipid oxidation and decreased EDV
. The effect on EDV of non-esterified fatty acids could be reversed by hype
rinsulinaemia.