Published online before print September 13, 2004, doi: 10.1161/01.CIR.0000142055.53122.FA
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(Circulation. 2004;110:1564-1571.)
© 2004 American Heart Association, Inc.
Coronary Heart Disease |
Circulating Mononuclear Cells in the Obese Are in a Proinflammatory State
From the Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, NY.
Correspondence to Paresh Dandona, MD, PhD, Diabetes-Endocrinology Center of Western New York, 3 Gates Circle, Buffalo, NY 14209. E-mail pdandona{at}kaleidahealth.org
Received December 16, 2003; de novo received February 18, 2004; revision received May 6, 2004; accepted May 7, 2004.
Background— In view of the increase in plasma concentrations of proinflammatory mediators tumor necrosis factor-
(TNF-), 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 
B (NF-B) binding to DNA in nuclear extracts was elevated (P<0.05) and the inhibitor of NFB-ß (IB-ß) 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-, and matrix metalloproteinase-9 (MMP-9) mRNA expression in the obese subjects (P<0.05). Plasma concentrations of MIF, IL-6, TNF-, 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- 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-B binding, a decrease in IB-ß, and an increase in the transcription of proinflammatory genes regulated by NF-B; (2) that plasma FFAs are a modulator of inflammation; and (3) that insulin resistance is a function of inflammatory mediators.
Key Words: obesity • inflammation • monocytes
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