Plaza-Florido Abel, Altmäe Signe, Esteban Francisco J, Cadenas-Sanchez Cristina, Aguilera Concepción M, Einarsdottir Elisabet, Katayama Shintaro, Krjutškov Kaarel, Kere Juha, Zaldivar Frank, Radom-Aizik Shlomit, Ortega Francisco B
PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, 18011, Granada, Spain.
Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Granada, Spain.
Pediatr Res. 2021 May;89(7):1687-1694. doi: 10.1038/s41390-020-01276-7. Epub 2020 Nov 23.
Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes. The underlying mechanisms for those differences are still unclear. This study aimed to analyze the whole-blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes.
Twenty-seven children with OW/OB (10.1 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein-cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers were additionally determined. Total blood RNA was analyzed by 5'-end RNA-sequencing.
Whole-blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. Thirty-two genes differentially expressed were linked to metabolism, mitochondrial, and immune functions.
The identified gene expression patterns related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity.
A distinct pattern of whole-blood transcriptome profile (RNA-seq) was identified in children with metabolic healthy overweight/obesity (MHO) compared to metabolic unhealthy overweight/obesity (MUO) phenotype. The most relevant genes in understanding the molecular basis underlying the MHO/MUO phenotypes in children could be: RREB1, FAM83E, SLC44A1, NRG1, TMC5, CYP3A5, TRIM11, and ADAMTSL2. The identified whole-blood transcriptome profile related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity.
超重/肥胖（OW/OB）的青少年人群在心脏代谢健康表型上存在异质性。这些差异的潜在机制仍不清楚。本研究旨在分析具有代谢健康超重/肥胖（MHO）和代谢不健康超重/肥胖（MUO）表型的儿童的全血转录组谱（RNA测序）。
纳入了来自ActiveBrains项目的27名超重/肥胖儿童（10.1±1.3岁，59%为男孩）。MHO被定义为不具备以下任何代谢综合征标准：空腹血糖升高、血清甘油三酯升高、高密度脂蛋白胆固醇降低以及收缩压或舒张压升高，而MUO被定义为呈现这些标准中的一项或多项。此外还测定了炎症标志物。通过5'端RNA测序分析全血RNA。
全血转录组分析显示，与MUO儿童相比，MHO儿童具有独特的基因表达模式。32个差异表达基因与代谢、线粒体和免疫功能相关。
所确定的与代谢、线粒体和免疫功能相关的基因表达模式有助于更好地理解为什么一部分人群尽管超重/肥胖但仍保持代谢健康。
与代谢不健康超重/肥胖（MUO）表型相比，在代谢健康超重/肥胖（MHO）儿童中鉴定出了独特的全血转录组谱（RNA测序）模式。在理解儿童MHO/MUO表型潜在分子基础方面最相关的基因可能是：RREB1、FAM83E、SLC44A1、NRG1、TMC5、CYP3A5、TRIM11和ADAMTSL2。所确定的与代谢、线粒体和免疫功能相关的全血转录组谱有助于更好地理解为什么一部分人群尽管超重/肥胖但仍保持代谢健康。
