Increasing plasma fatty acids elevates F2-isoprostanes in humans: implications for the cardiovascular risk factor cluster.
OBJECTIVE
To determine whether raised concentrations of non-esterified fatty acids (NEFAs) may contribute to the cardiovascular risk factor cluster by increasing oxidative stress in vivo.


METHODS
Plasma and urine F2-isoprostanes, biomarkers of oxidative stress, were measured after an overnight fast and during a 4 h infusion of Intralipid and heparin to increase NEFAs in 10 obese hypertensive patients with and 12 healthy normotensive individuals without evidence of insulin resistance. A time-control group of nine healthy normotensive individuals received saline and heparin.


RESULTS
Plasma F2-isoprostanes increased more in obese hypertensive individuals than in lean normotensive individuals after 2 h (14.9 +/- 2.8 ng/ml compared with 4.6 +/- 2.8 ng/ml; P < 0.05) but not after 4 h (10.3 +/- 2.5 ng/ml compared with 8.1 +/- 4.1 ng/ml; NS) of the Intralipid and heparin infusion. When obese and lean individuals were combined, plasma (+9.1 +/- 2.5 ng/ml; P < 0.05) and urine (+0.7 +/- 0.3 ng/mg creatinine; P < 0.05) F2-isoprostanes increased by about 20% after 4 h of Intralipid and heparin, whereas plasma F2-isoprostanes decreased by approximately 20% (-9.7 +/- 4.5 ng/ml; P < 0.05) after 4 h of saline and heparin. When individuals from both infusions were combined, the correlation between changes in plasma NEFAs and F2-isoprostanes after 4 h persisted after controlling for changes in triglyceride concentrations (partial r = 0.49; P < 0.01), whereas the correlation between changes in triglycerides and F2-isoprostanes did not persist after controlling for changes in NEFA concentrations (partial r = 0.33, NS).


CONCLUSIONS
The findings indicate that an acute increase in plasma lipids increases the concentration of F2-isoprostanes, biomarkers of oxidative stress, especially in obese hypertensive individuals. The observations raise the possibility that increased concentrations of NEFAs contribute to the cardiovascular risk factor cluster through oxidative-stress-sensitive mechanisms.
Stojiljkovic
Milos P
MP
Department of Pharmacology and Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Lopes
Heno F
HF
Zhang
Da
D
Morrow
Jason D
JD
Goodfriend
Theodore L
TL
Egan
Brent M
BM
D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology; D016000:Cluster Analysis; D004338:Drug Combinations; D028441:F2-Isoprostanes / Q000097:blood* / Q000652:urine; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005227:Fatty Acids / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000652:urine; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D012016:Reference Values; D012307:Risk Factors; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
D004338:Drug Combinations; D028441:F2-Isoprostanes; D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D012965:Sodium Chloride; D006493:Heparin