Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Export

@article{citeulike:239492, abstract = {To test the possible acute proinflammatory effects of fatty acids, we induced an increase in plasma free fatty acid (FFA) concentrations after a lipid and heparin infusion for 4 h in 10 healthy subjects. We determined the nuclear factor-kappaB (NF-kappaB) binding activity in mononuclear cells (MNCs), the p65 subunit of NF-kappaB, reactive oxygen species (ROS) generation by MNC, and polymorphonuclear leukocytes (PMN). Brachial artery reactivity, using postischemic flow-mediated dilation, was also measured. NF-kappaB binding activity in the MNC nuclear extracts increased to 163 +/- 17\% and 144 +/- 14\% as compared with basal levels at 2 and 4 h (P < 0.005) and remained elevated (P < 0.05) at 6 h (2 h after cessation of lipid infusion). NF-kappaB p65 subunit protein expression in MNC homogenates also increased at 2, 4, and 6 h (P < 0.05). ROS generation by PMNs increased significantly at 2 and 4 h (P < 0.005), whereas that by MNCs increased at 4 h (P < 0.05). Plasma macrophage migration inhibitory factor increased at 2 (P < 0.05) and 4 h (P < 0.005), respectively, and declined to baseline at 6 h. The postischemic flow-mediated dilation of brachial artery decreased from 6.3 +/- 1.1\% at baseline to 4.3 +/- 1.9\% and 2.7 +/- 2.1\% (P < 0.01) at 2, 4, and 6 h, respectively. We conclude that an increase in FFA concentration induces oxidative stress and has a proinflammatory effect; it also impairs postischemic flow-mediated vasodilation of the brachial artery.}, address = {Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York 14209, USA.}, author = {Tripathy, D. and Mohanty, P. and Dhindsa, S. and Syed, T. and Ghanim, H. and Aljada, A. and Dandona, P.}, citeulike-article-id = {239492}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/14633847}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=14633847}, issn = {0012-1797}, journal = {Diabetes}, keywords = {endothelialfunction, endothelium, ffa, inflammation, mnc, mononuclear, vascular}, month = {December}, number = {12}, pages = {2882--2887}, posted-at = {2005-06-28 15:10:18}, priority = {2}, title = {Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/14633847}, volume = {52}, year = {2003} }

TY - JOUR ID - citeulike:239492 L3 - citeulike-article-id:239492 N2 - To test the possible acute proinflammatory effects of fatty acids, we induced an increase in plasma free fatty acid (FFA) concentrations after a lipid and heparin infusion for 4 h in 10 healthy subjects. We determined the nuclear factor-kappaB (NF-kappaB) binding activity in mononuclear cells (MNCs), the p65 subunit of NF-kappaB, reactive oxygen species (ROS) generation by MNC, and polymorphonuclear leukocytes (PMN). Brachial artery reactivity, using postischemic flow-mediated dilation, was also measured. NF-kappaB binding activity in the MNC nuclear extracts increased to 163 +/- 17% and 144 +/- 14% as compared with basal levels at 2 and 4 h (P < 0.005) and remained elevated (P < 0.05) at 6 h (2 h after cessation of lipid infusion). NF-kappaB p65 subunit protein expression in MNC homogenates also increased at 2, 4, and 6 h (P < 0.05). ROS generation by PMNs increased significantly at 2 and 4 h (P < 0.005), whereas that by MNCs increased at 4 h (P < 0.05). Plasma macrophage migration inhibitory factor increased at 2 (P < 0.05) and 4 h (P < 0.005), respectively, and declined to baseline at 6 h. The postischemic flow-mediated dilation of brachial artery decreased from 6.3 +/- 1.1% at baseline to 4.3 +/- 1.9% and 2.7 +/- 2.1% (P < 0.01) at 2, 4, and 6 h, respectively. We conclude that an increase in FFA concentration induces oxidative stress and has a proinflammatory effect; it also impairs postischemic flow-mediated vasodilation of the brachial artery. IS - 12 JF - Diabetes SN - 0012-1797 AD - Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York 14209, USA. EP - 2887 TI - Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. VL - 52 SP - 2882 KW - endothelialfunction KW - endothelium KW - ffa KW - inflammation KW - mnc KW - mononuclear KW - vascular AU - Tripathy, D AU - Mohanty, P AU - Dhindsa, S AU - Syed, T AU - Ghanim, H AU - Aljada, A AU - Dandona, P PY - 2003/12// UR - http://view.ncbi.nlm.nih.gov/pubmed/14633847 ER -