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超重/肥胖儿童的心肺适能以及与脑和心血管健康相关的靶向蛋白质组学

Cardiorespiratory fitness and targeted proteomics involved in brain and cardiovascular health in children with overweight/obesity.

作者信息

Plaza-Florido Abel, Rodriguez-Ayllon Maria, Altmäe Signe, Ortega Francisco B, Esteban-Cornejo Irene

机构信息

Faculty of Sport Sciences, University of Granada, Department of Physical and Sports Education; Sport and Health University Research Institute (iMUDS), Granada, Spain.

Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California at Irvine, Irvine, USA.

出版信息

Eur J Sport Sci. 2023 Oct;23(10):2076-2085. doi: 10.1080/17461391.2023.2167237. Epub 2023 Feb 23.

DOI:10.1080/17461391.2023.2167237
PMID:36622372
Abstract

Cardiorespiratory fitness (CRF) is inversely associated with cardiovascular disease (CVD) risk factors and brain health impairments. However, the molecular mechanisms linking CRF to health in children are poorly understood. We aimed to examine protein levels related to brain health and CVD in plasma of fit compared to unfit children with overweight/obesity (OW/OB). Eighty-seven children with OW/OB (10.08 ± 1.1 years, 59% boys) from the ActiveBrains project were included. CRF was measured by performing a treadmill test, and children were categorized into fit or unfit. Targeted proteomics in plasma was performed using Olink's proximity extension assay technology of Neurology panel in the whole sample and of Cardiovascular panel in a subsample. Sixteen proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) were differentially expressed between fit and unfit children with OW/OB after adjusting for sex, maturational status, and body mass index. However, statistically significant differences disappeared after applying FDR correction. Potential candidate proteins related to CRF levels in children with OW/OB were detected, being involved in several biological processes such as neurogenesis, immune/inflammatory response, signal transduction, platelet activation. Nevertheless, these preliminary findings should be confirmed or contrasted in future studies using larger sample sizes, longitudinal and experimental designs.The molecular mechanisms underlying the link of cardiorespiratory fitness (CRF) with cardiovascular and brain health in children with overweight/obesity (OW/OB) are poorly understood.Targeted proteomic analysis revealed differentially expressed proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) in plasma of "Fit" compared to "Unfit" children with OW/OB. These proteins are involved in several biological processes such as immune/inflammatory response, neurogenesis, signal transduction, and cellular metabolic process.Longitudinal and experimental studies are warranted to reveal how improvements in CRF are related to changes in circulating levels of the abovementioned proteins and how they might reduce cardiovascular diseases risk factors and brain health impairments later in life.

摘要

心肺适能(CRF)与心血管疾病(CVD)风险因素及脑健康损害呈负相关。然而,CRF与儿童健康之间的分子机制尚不清楚。我们旨在研究超重/肥胖(OW/OB)的健康儿童与不健康儿童血浆中与脑健康和CVD相关的蛋白质水平。纳入了来自“活跃大脑”项目的87名OW/OB儿童(10.08±1.1岁,59%为男孩)。通过进行跑步机测试来测量CRF,并将儿童分为健康组或不健康组。在整个样本中使用Olink神经学面板的邻近延伸分析技术,在一个子样本中使用心血管面板的邻近延伸分析技术对血浆进行靶向蛋白质组学分析。在调整性别、成熟状态和体重指数后,16种蛋白质(PLXNB3、sFRP3、CLEC1B、RSPO1、Gal8、CLEC10A、GCP5、MDGA1、CTSC、LAT、IL4RA、PRSS27、CXCL1、Gal9、MERTK和GT)在OW/OB的健康儿童与不健康儿童之间存在差异表达。然而,应用错误发现率(FDR)校正后,统计学上的显著差异消失了。在OW/OB儿童中检测到了与CRF水平相关的潜在候选蛋白质,它们参与了神经发生、免疫/炎症反应、信号转导、血小板激活等多种生物学过程。尽管如此,这些初步发现应在未来使用更大样本量、纵向和实验设计的研究中得到证实或对比。超重/肥胖(OW/OB)儿童中心肺适能(CRF)与心血管和脑健康之间联系的分子机制尚不清楚。靶向蛋白质组学分析显示,与OW/OB的“不健康”儿童相比,“健康”儿童血浆中存在差异表达的蛋白质(PLXNB3、sFRP3、CLEC1B、RSPO1、Gal8、CLEC10A,、GCP5、MDGA1、CTSC、LAT、IL4RA、PRSS27、CXCL1、Gal9、MERTK和GT)。这些蛋白质参与了免疫/炎症反应、神经发生、信号转导和细胞代谢过程等多种生物学过程。有必要进行纵向和实验研究,以揭示CRF的改善如何与上述蛋白质循环水平的变化相关,以及它们如何在以后的生活中降低心血管疾病风险因素和脑健康损害。

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