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/m 2 ) and normal-weight control (n=16; BMI=23.8±1.9 kg/m 2 ) subjects. Nuclear factor κB (NF-κB) binding to DNA in nuclear extracts was elevated ( P P P 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.