Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects.
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.
Tripathy
Devjit
D
Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York 14209, USA.
Mohanty
Priya
P
Dhindsa
Sandeep
S
Syed
Tufail
T
Ghanim
Husam
H
Aljada
Ahmad
A
Dandona
Paresh
P
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
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