Effect of weight loss on proinflammatory state of mononuclear cells in obese women.
In order to investigate whether weight loss can lead to improvement of the mononuclear cell (MNC) proinflammatory state, 21 nondiabetic obese women with mean age 34+/-2 years (mean+/-s.e.m.) and BMI 32.5+/-1.2 kg/m2 were enrolled in a 12-week caloric restriction and light exercise-based weight loss program. Ten lean women served as controls. Reverse transcription-PCR of proinflammatory cytokines and adipocytokines as well as homeostasis model assessment of insulin resistance (HOMA-IR) were determined before and after weight reduction. Nuclear factor kappaB (NF-kappaB) binding to DNA and inhibitors of NF-kappaB (IkappaB-alpha and IkappaB-beta) obtained from peripheral MNCs were measured. Overall, subjects lost a mean of 4.0+/-0.4 kg (5.0+/-0.3% of their initial body weight) (P<0.01). In addition to significant reductions in BMI, fasting glucose and insulin concentrations, mean serum high-sensitivity C-reactive protein (hs-CRP), migration inhibitor factor (MIF), leptin and visfatin levels decreased by 49.0, 66.6, 17.2, and 50.2%, respectively (all P<0.05), while adiponectin concentrations rose by 33.9% (P<0.05). The DNA binding of the transcriptionally active NF-kappaB from (p65/p50) decreased by 38.1% (P<0.05). Elevated levels of mRNA of NF-kappaB related proinflammatory genes, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), MIF, and matrix metalloproteinase-9 (MMP-9), decreased significantly after weight loss. Although mRNA expression of Rel-A, p105, IkappaB-alpha, IkappaB-beta decreased significantly, their protein levels did not change after weight loss. As a group, NF-kappaB binding activity correlated with HOMA-IR (r=0.332, P=0.049) and marginally with values of BMI (r=0.308, P=0.059). In conclusion, weight loss by 5% of initial weight in nondiabetic obese women led to significant improvement in activated intranuclear NF-kappaB binding as well as several transcriptions of proinflammatory genes regulated by NF-kappaB.
Sheu
Wayne H-H
WH
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan. whhsheu@vghtc.gov.tw
Chang
Tzu-Ming
TM
Lee
Wen-Jane
WJ
Ou
Hsiu-Chung
HC
Wu
Ching-Mei
CM
Tseng
Li-Nien
LN
Lang
Hui-Fen
HF
Wu
Cheng-Shiu
CS
Wan
Chu-Jen
CJ
Lee
I-Te
IT
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D019746:Intramolecular Oxidoreductases / Q000097:blood; D020738:Leptin / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000097:blood; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood; D009765:Obesity / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015431:Weight Loss / Q000502:physiology*
D001786:Blood Glucose; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D002097:C-Reactive Protein; D054409:Nicotinamide Phosphoribosyltransferase; D020780:Matrix Metalloproteinase 9; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human