Mental stress is known to decrease systemic vascular resistance and increas
e muscle blood flow and to acutely enhance insulin-mediated glucose disposa
l in healthy humans. These effects are abolished in obese patients. We ther
efore proposed the hypothesis that elevated free fatty acid levels may be r
esponsible for the abnormal responses to mental stress in obesity by inhibi
ting endothelial cell function. To test this hypothesis, we studied group o
f eight lean females during a hyperinsulinemic clamp study with and without
Lipid infusion. A 30-min mental stress was applied during 30 min after 150
min of hyperinsulinemia. In the study without lipid infusion, mental stres
s increased heart rate by 26.5%, blood pressure by 7.9%, and cardiac index
(measured with thoracic bioimpedance) by 35.9%; it decreased systemic vascu
lar resistance by 21.9% and increased insulin-mediated glucose disposal by
18.9%. During lipid infusion, the increase in heart rate was not affected,
but the increase in cardiac index, the decrease in systemic vascular resist
ance, and the increase in insulin-mediated glucose disposal were all inhibi
ted. In contrast, the rise in blood pressure was increased about 2-fold (co
ntrol plus 6 mm Hg vs. lipid plus 13 mm Hg, P < 0.01). These results indica
te that lipid inhibits the stimulation of glucose uptake and enhances the p
resser effect of mental stress, presumably by altering endothelial cell fun
ction.