title: Effect of weight loss on proinflammatory state of mononuclear cells in obese women.
abstract: 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.
authors: 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
authors: Wayne H-H
authors: WH
authors: Sheu
authors: Tzu-Ming
authors: TM
authors: Chang
authors: Wen-Jane
authors: WJ
authors: Lee
authors: Hsiu-Chung
authors: HC
authors: Ou
authors: Ching-Mei
authors: CM
authors: Wu
authors: Li-Nien
authors: LN
authors: Tseng
authors: Hui-Fen
authors: HF
authors: Lang
authors: Cheng-Shiu
authors: CS
authors: Wu
authors: Chu-Jen
authors: CJ
authors: Wan
authors: I-Te
authors: IT
authors: Lee
mesh_terms: 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*
chemical_list: 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