Circulating mononuclear cells in the obese are in a proinflammatory state

Background - In view of the increase in plasma concentrations of proinflammatory mediators tumor necrosis factor-α (TNF-α), 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 κB (NF-κB) binding to DNA in nuclear extracts was elevated (P<0.05) and the inhibitor of NFκB-β (1κB-β) 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-α, and matrix metalloproteinase-9 (MMP-9) mRNA expression in the obese subjects (P<0.05). Plasma concentrations of MIF, IL-6, TNF-α, 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-α 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-κB binding, a decrease in IκB-β, and an increase in the transcription of proinflammatory genes regulated by NF-κB; (2) that plasma FFAs are a modulator of inflammation; and (3) that insulin resistance is a function of inflammatory mediators.