title: Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects.
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.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York 14209, USA.
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
authors.forename: Priya
authors.initials: P
authors.lastname: Mohanty
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dhindsa
authors.forename: Tufail
authors.initials: T
authors.lastname: Syed
authors.forename: Husam
authors.initials: H
authors.lastname: Ghanim
authors.forename: Ahmad
authors.initials: A
authors.lastname: Aljada
authors.forename: Paresh
authors.initials: P
authors.lastname: Dandona
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007328:Insulin / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051996:Transcription Factor RelA; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D051996:Transcription Factor RelA; D014280:Triglycerides