Downregulation of genes involved in NFκB activation in peripheral blood mononuclear cells after weight loss is associated with the improvement of insulin sensitivity in individuals with the metabolic syndrome:: the GENOBIN study
Downregulation of genes involved in NFκB activation in peripheral blood mononuclear cells after weight loss is associated with the improvement of insulin sensitivity in individuals with the metabolic syndrome:: the GENOBIN study
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DOI：
10.1007/s00125-008-1132-7
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发表时间：
2008-11-01
期刊：
影响因子：
8.2
通讯作者：
Uusitupa, M.
中科院分区：
文献类型：
--
作者：
de Mello, V. D. F.;Kolehmainen, M.;Uusitupa, M.
转录因子核因子- κ B （NF κ B）参与炎症反应、肥胖和代谢综合征，而免疫细胞似乎在介导胰岛素抵抗中发挥核心作用，可以作为研究炎症及其与胰岛素抵抗关系的模型。在患有代谢综合征的超重参与者的外周血单核细胞中，我们评估了(1)饮食诱导的体重减轻对参与NF κ B激活的基因表达的影响，(2)它们与胰岛素敏感性的关系。研究的基因有：TNF受体TNFRSF1A和TNFRSF1B，以及IL1R1、TLR4、TLR2、ICAM1、CCL5和IKBKB。方法我们分析了34名伴有糖代谢异常和代谢综合征的超重参与者的数据，他们被随机分为减肥组（n=24）和对照组（n=10），为期33周。实时荧光定量PCR检测mRNA表达。采用IVGTT和OGTT评估胰岛素和葡萄糖稳态。结果总体而言，研究基因在减肥干预后下调。TLR4、TLR2、CCL5和TNFRSF1A mRNA表达变化与胰岛素敏感性指数升高相关，与腰围变化无关（p < 0.05）。在减肥组中，IKBKB表达的变化与大部分基因表达的变化相关。这些结果表明，CCL5、TLR2和TLR4以及TNFRSF1A编码的蛋白可能与肥胖症和代谢综合征的胰岛素抵抗状态有关。试验注册：ClinicalTrials.gov NCT 00621205。
Aims/hypothesis The transcription factor nuclear factor-kappa-B (NF kappa B) is implicated in inflammatory responses, obesity and the metabolic syndrome, while immune cells appear to play a central role in mediating insulin resistance and can be used as a model to study inflammation and its relationship with insulin resistance. In peripheral blood mononuclear cells of overweight participants with the metabolic syndrome, we evaluated (1) the effect of diet-induced weight loss on the expression of genes involved in NF kappa B activation and (2) their association with insulin sensitivity. The genes studied were: TNF receptors TNFRSF1A and TNFRSF1B, and IL1R1, TLR4, TLR2, ICAM1, CCL5 and IKBKB.Methods We analysed data from 34 overweight participants with abnormal glucose metabolism and the metabolic syndrome, who were randomised to a weight-reduction (n=24) or control group (n=10) for 33 weeks. The mRNA expression was measured using real-time PCR. Measures of insulin and glucose homeostasis were assessed by IVGTT and OGTT.Results In general, the genes studied were downregulated after weight loss intervention. The changes in TLR4, TLR2, CCL5 and TNFRSF1A mRNA expression were associated with an increase in insulin sensitivity index independently of the change in waist circumference (p < 0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group.Conclusions/interpretation These results suggest that proteins encoded by CCL5, TLR2 and TLR4, and TNFRSF1A might contribute to insulin-resistant states that characterise obesity and the metabolic syndrome.Trial registration: ClinicalTrials.gov NCT 00621205.