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

• Published in: Diabetes (New York, N.Y.) Vol. 52; no. 12; pp. 2882 - 2887
• Main Authors: Tripathy, Devjit, Mohanty, Priya, Dhindsa, Sandeep, Syed, Tufail, Ghanim, Husam, Aljada, Ahmad, Dandona, Paresh
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.2003
• Subjects: Adult; Anticoagulants; Associated diseases and complications; Biological and medical sciences; Blood; Brachial Artery - physiology; Cytokines; Diabetes; Diabetes mellitus; Diabetes research; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Fatty acid metabolism; Fatty acids; Fatty Acids, Nonesterified - blood; Female; Humans; Inflammation; Inflammation - etiology; Insulin - blood; Insulin resistance; Kinases; Leukocytes; Lipids; Male; Medical sciences; Monocytes - metabolism; Neutrophils - metabolism; NF-kappa B - metabolism; Oxidative stress; Physiological aspects; Plasma; Reactive Oxygen Species - metabolism; Reference Values; Thiobarbituric Acid Reactive Substances - metabolism; Transcription Factor RelA; Triglycerides - blood; Tumor necrosis factor-TNF; Vasodilation; Veins & arteries; United States; Endocrinopathy; Human; Reactivity; Diabetes mellitus; Lipids; Inflammation; Free fatty acid
• DOI: 10.2337/diabetes.52.12.2882
• ISSN: 0012-1797

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 Aljada and Paresh Dandona From the Division of Endocrinology, Diabetes and Metabolism, State University of New York and Kaleida Health, Buffalo, New York Address correspondence and reprint requests to Paresh Dandona, MD, PhD, Diabetes-Endocrinology Center of Western New York, 3 Gates Circle, Buffalo, NY 14209. E-mail: pdandona{at}kaleidahealth.org 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. CRP, C-reactive protein ELISA, enzyme-linked immunosorbent assay FFA, free fatty acid ICAM, intracellular adhesion molecule IκB, inhibitor κB IKK-β, IκB kinase-β MCP-1, monocyte chemoattractant protein MIF, macrophage migration inhibitory factor MNC, mononuclear cell NF-κB, nuclear factor-κB PMN, polymorphonuclear leukocyte ROS, reactive oxygen species sICAM, soluble ICAM TBARS, thiobarbituric acid reactive substances TNF-α, tumor necrosis factor-α Footnotes Accepted September 12, 2003. Received March 5, 2003. DIABETES