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

Clin Sci (Lond). 2000 Sep;99(3):169-74. doi: 10.1042/cs0990169.

Abstract

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 ml x min(-1) x 100 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 ml x min(-1) x 100 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 micromol/l (P < 0.001), while hyperinsulinaemiadid 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.

MeSH terms

  • Adult
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Fat Emulsions, Intravenous / pharmacology
  • Fatty Acids, Nonesterified / blood
  • Fatty Acids, Nonesterified / physiology*
  • Female
  • Forearm / blood supply
  • Glucose Clamp Technique
  • Humans
  • Hyperinsulinism / blood
  • Hyperinsulinism / physiopathology*
  • Male
  • Malondialdehyde / blood
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Triglycerides / blood
  • Vasodilation / drug effects
  • Vasodilation / physiology*
  • Vasodilator Agents / pharmacology

Substances

  • Fat Emulsions, Intravenous
  • Fatty Acids, Nonesterified
  • Triglycerides
  • Vasodilator Agents
  • Malondialdehyde