Plaza-Florido Abel, Anguita-Ruiz Augusto, Esteban Francisco J, Aguilera Concepción M, Labayen Idoia, Reitzner Stefan Markus, Sundberg Carl Johan, Radom-Aizik Shlomit, Ortega Francisco B, Altmäe Signe
Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.
Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California, Irvine, California, United States.
Physiol Genomics. 2025 Feb 1;57(2):91-102. doi: 10.1152/physiolgenomics.00059.2024. Epub 2025 Jan 3.
We examined the effects of a 20-wk exercise intervention on whole blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). Twenty-three children (10.05 ± 1.39 yr, 56% girls) with OW/OB were randomized to either a 20-wk exercise intervention [exercise group (EG); = 10; 4 boys/6 girls] or to usual lifestyle [control group (CG); = 13; 6 boys/7 girls]. Whole blood genome-wide methylome (CpG sites) analysis using Infinium Methylation EPIC array and transcriptome analysis using RNA-seq (STRT2 protocol) were performed. Exercise-induced modifications in DNA methylation at 485 and 386 CpGs sites in boys and girls, respectively. These CpG sites are mapped to loci enriched in distinct gene pathways related to metabolic diseases, fatty acid metabolism, and immune function. In boys, changes in the DNA methylation of 87 CpG sites (18% of the 485 CpGs sites altered by exercise) were associated with changes in the gene expression levels of 51 genes also regulated by exercise. Among girls, changes in DNA methylation at 46 CpG sites (12% of the initial 386 significant CpGs) were associated with changes in the expression levels of 30 exercise-affected genes. Genes affected by exercise that were associated with DNA methylation are related to obesity, metabolic syndrome, and inflammation. Multiomics analysis of whole blood samples from children with OW/OB suggests that gene expression response to exercise may be modulated by DNA methylation and involve gene pathways related to metabolism and immune functions. This study pioneers the exploration into the effects of exercise on whole blood genome-wide DNA methylation patterns and its association with changes in transcriptome profiles in children with overweight/obesity. Exercise potentially impacts molecular pathways involved in metabolism and immune functions in children with overweight/obesity (sex-specific responses) through the modification of epigenetic and transcriptomic profiles. Our preliminary results provide initial steps to understand better the molecular mechanisms underlying cardiometabolic benefits of exercise in children with overweight/obesity.
我们研究了为期20周的运动干预对超重/肥胖（OW/OB）男孩和女孩全血基因组范围内DNA甲基化特征的影响及其与运动诱导的基因表达谱变化的关联。23名超重/肥胖儿童（10.05±1.39岁，56%为女孩）被随机分为两组，一组接受为期20周的运动干预[运动组（EG）；n = 10；4名男孩/6名女孩]，另一组保持通常的生活方式[对照组（CG）；n = 13；6名男孩/7名女孩]。使用Infinium甲基化EPIC芯片进行全血基因组范围内的甲基化组（CpG位点）分析，并使用RNA测序（STRT2方案）进行转录组分析。运动分别在男孩和女孩的485个和386个CpG位点诱导了DNA甲基化修饰。这些CpG位点映射到与代谢疾病、脂肪酸代谢和免疫功能相关的不同基因途径富集的基因座。在男孩中，87个CpG位点（运动改变的485个CpG位点中的18%）的DNA甲基化变化与51个同样受运动调节的基因的表达水平变化相关。在女孩中，46个CpG位点（最初386个显著CpG位点中的12%）的DNA甲基化变化与30个受运动影响的基因的表达水平变化相关。受运动影响且与DNA甲基化相关的基因与肥胖、代谢综合征和炎症有关。对超重/肥胖儿童全血样本的多组学分析表明，运动诱导的基因表达反应可能受DNA甲基化调节，并涉及与代谢和免疫功能相关的基因途径。本研究率先探索了运动对超重/肥胖儿童全血基因组范围内DNA甲基化模式的影响及其与转录组谱变化的关联。运动可能通过改变表观遗传和转录组谱影响超重/肥胖儿童（性别特异性反应）中参与代谢和免疫功能的分子途径。我们的初步结果为更好地理解运动对超重/肥胖儿童心脏代谢益处的潜在分子机制提供了初步线索。
