The Impact of Childhood Obesity on Inflammation, Innate Immune Cell Frequency, and Metabolic MicroRNA Expression
The Impact of Childhood Obesity on Inflammation, Innate Immune Cell Frequency, and Metabolic MicroRNA Expression
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DOI：
10.1210/jc.2013-3529
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发表时间：
2014-03-01
影响因子：
5.8
通讯作者：
O'Shea, Donal
中科院分区：
文献类型：
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作者：
Carolan, Eirin;Hogan, Andrew E.;O'Shea, Donal
背景资料：肥胖的特征是慢性炎症、免疫失调和基因表达改变，与2型糖尿病和心血管疾病相关。这些变化发生在儿童肥胖的程度是不完全defined.Aims和方法：其目的是研究儿童肥胖对免疫细胞频率，巨噬细胞活化，细胞因子的产生，代谢基因表达的特定调节剂的影响。采用实时PCR、ELISA和流式细胞术对29名肥胖和20名非肥胖儿童的外周血进行分析。结果：两组的空腹血糖相似，但肥胖受试者的胰岛素抵抗程度较高（胰岛素抵抗评估的稳态模型，4.8 vs 0.84; P <0.001）。可溶性CD 163是巨噬细胞极化为促炎性的标志物，肥胖儿童的可溶性CD 163水平高于非肥胖儿童（135 vs 105 ng/mL; P = 0.03）。肥胖儿童中不变的自然杀伤T细胞减少（CD 3 T细胞，0.31 vs 0.53%; P = 0.001）。细胞因子分析显示，与非肥胖儿童相比，肥胖儿童的TNF-α（6.7 vs 5.1 pg/mL; P = .01）和瘦素（1186 vs 432 pg/mL; P < .001）显著升高，脂联素（884 vs 1321 pg/mL; P = .001）降低。刺激肥胖儿童的外周血单核细胞导致更高水平的IL-1 β（2100 vs 1500 pg/mL; P = 0.018）。肥胖儿童microRNA 33 a的表达增加了4倍（P = 0.001），microRNA 33 b的表达增加了3倍（P = 0.017）。结论：儿童肥胖与免疫细胞频率、炎症环境和代谢基因表达调控的变化有关。这些变化与成年期代谢疾病的发病有因果关系，并表明肥胖儿童未来发展为2型糖尿病和早发心血管疾病的轨迹。
Background: Obesity is characterized by chronic inflammation, immune dysregulation, and alteration of gene expression, associated with type 2 diabetes mellitus and cardiovascular disease. The degree to which these changes occur in childhood obesity is not fully defined.Aims and Methods: The aim was to investigate the effect of childhood obesity on immune cell frequency, macrophage activation, cytokine production, and specific regulators of metabolic gene expression. Profiling was performed on peripheral blood from 29 obese and 20 nonobese children using real-time PCR, ELISA, and flow cytometry.Results: Fasting glucose was similar in both groups, but there was a higher degree of insulin resistance in obese subjects (homeostasis model of assessment for insulin resistance, 4.8 vs 0.84; P < .001). Soluble CD163, a marker of macrophage polarization to a proinflammatory profile, was elevated in the obese compared to nonobese children (135 vs 105 ng/mL; P = .03). Invariant natural killer T cells were reduced in the obese children (CD3 T cells, 0.31 vs 0.53%; P = .001). Cytokine profiling revealed significantly elevated TNF-alpha (6.7 vs 5.1 pg/mL; P = .01) and leptin (1186 vs 432 pg/mL; P < .001) and reduced adiponectin (884 vs 1321 pg/mL; P = .001) in obese compared to nonobese children. Stimulation of peripheral blood mononuclear cells from obese children resulted in higher levels of IL-1 beta (2100 vs 1500 pg/mL; P = .018). There was a 4-fold increase in expression of microRNA33a (P = .001) and a 3-fold increase in microRNA33b (P = .017) in obese children.Conclusion: Childhood obesity is associated with changes in immune cell frequency, inflammatory environment, and regulation of metabolic gene expression. These changes have been causally linked to the onset of metabolic disease in adulthood and suggest the future trajectory of obese children to the development of type 2 diabetes mellitus and premature cardiovascular disease.