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. DESIGN AND 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.
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. DESIGN AND 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 hypertensivepatients 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.
Authors: Sean S Davies; Eric J Brantley; Paul A Voziyan; Venkataraman Amarnath; Irene Zagol-Ikapitte; Olivier Boutaud; Billy G Hudson; John A Oates; L Jackson Roberts Journal: Biochemistry Date: 2006-12-06 Impact factor: 3.162
Authors: B J Novak; D R Blake; S Meinardi; F S Rowland; A Pontello; D M Cooper; P R Galassetti Journal: Proc Natl Acad Sci U S A Date: 2007-09-25 Impact factor: 11.205