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-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.


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.
Ghanim
Husam
H
Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo, NY, USA.
Aljada
Ahmad
A
Hofmeyer
Deborah
D
Syed
Tufail
T
Mohanty
Priya
P
Dandona
Paresh
P
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics; D002467:Cell Nucleus / Q000737:chemistry; D004247:DNA / Q000097:blood; D005215:Fasting / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000097:blood / Q000235:genetics; D007249:Inflammation / Q000097:blood* / Q000209:etiology / Q000235:genetics; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D019255:NADPH Oxidases; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis / Q000097:blood; D009765:Obesity / Q000097:blood* / Q000150:complications; D010750:Phosphoproteins / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D002097:C-Reactive Protein; D004247:DNA; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D020780:Matrix Metalloproteinase 9