Thu, 21 Aug 2008 15:29:11 BST CiteULike: amromeo's Hofmeyer http://www.citeulike.org/user/amromeo/author/Hofmeyer CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/amromeo/article/2683767 <i>Circulation, Vol. 110, No. 12. (21 September 2004), pp. 1564-1571.</i><br /><br />Background-- In view of the increase in plasma concentrations of proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP) in obesity, we investigated whether peripheral blood mononuclear cells (MNC) from obese subjects are in a proinflammatory state. Methods and Results-- MNC were prepared from fasting blood samples of obese (n=16; body mass index [BMI]=37.7+/-5.0 kg/m2) and normal-weight control (n=16; BMI=23.8+/-1.9 kg/m2) subjects. Nuclear factor kappaB (NF-kappaB) binding to DNA in nuclear extracts was elevated (P<0.05) and the inhibitor of NFkappaB-beta (IkappaB-beta) was significantly lower (P<0.001) in the obese group. Reverse transcription-polymerase chain reaction revealed elevated levels of migration inhibitor factor (MIF), IL-6, TNF-alpha, and matrix metalloproteinase-9 (MMP-9) mRNA expression in the obese subjects (P<0.05). Plasma concentrations of MIF, IL-6, TNF-alpha, MMP-9, and CRP were also significantly higher. Plasma glucose, insulin, and free fatty acids (FFAs) were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Plasma FFA concentration related significantly to BMI, IL-6, and TNF-alpha mRNA expression and plasma CRP levels but not to HOMA-IR. On the other hand, the inflammatory mediators were significantly related to BMI and HOMA-IR. Conclusions-- These data show (1) for the first time that MNC in obesity are in a proinflammatory state with an increase in intranuclear NF-kappaB binding, a decrease in IkappaB-beta, and an increase in the transcription of proinflammatory genes regulated by NF-kappaB; (2) that plasma FFAs are a modulator of inflammation; and (3) that insulin resistance is a function of inflammatory mediators. 10.1161/01.CIR.0000142055.53122.FA Circulating Mononuclear Cells in the Obese Are in a Proinflammatory State Husam Ghanim Ahmad Aljada Deborah Hofmeyer Tufail Syed Priya Mohanty Paresh Dandona doi:10.1161/01.CIR.0000142055.53122.FA Circulation, Vol. 110, No. 12. (21 September 2004), pp. 1564-1571. 2008-04-17T23:10:03-00:00 2004 Circulation 110 12 1564 1571 ccr2 inflammation macrophage monocyte nfkb obese obesity