Elevation of Free Fatty Acids Induces Inflammation and Impairs Vascular Reactivity in Healthy Subjects

Devjit Tripathy, Priya Mohanty, Sandeep Dhindsa, Tufail Syed, Husam Ghanim, Ahmad Aliada, Paresh Dandona

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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-κB (NF-κB) binding activity in mononuclear cells (MNCs), the p65 subunit of NF-κB, reactive oxygen species (ROS) generation by MNC, and polymorphonuclear leukocytes (PMN). Brachial artery reactivity, using postischemic flow-mediated dilation, was also measured. NF-κB 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-κB 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.

Original languageEnglish (US)
Pages (from-to)2882-2887
Number of pages6
JournalDiabetes
Volume52
Issue number12
DOIs
StatePublished - Dec 1 2003

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Tripathy, D., Mohanty, P., Dhindsa, S., Syed, T., Ghanim, H., Aliada, A., & Dandona, P. (2003). Elevation of Free Fatty Acids Induces Inflammation and Impairs Vascular Reactivity in Healthy Subjects. Diabetes, 52(12), 2882-2887. https://doi.org/10.2337/diabetes.52.12.2882