Understanding the response to endurance exercise using a systems biology approach: combining blood metabolomics, transcriptomics and miRNomics in horses.
Understanding the response to endurance exercise using a systems biology approach: combining blood metabolomics, transcriptomics and miRNomics in horses.
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DOI：
10.1186/s12864-017-3571-3
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发表时间：
2017-02-17
期刊：
影响因子：
4.4
通讯作者：
Le Moyec L
中科院分区：
文献类型：
--
作者：
Mach N;Ramayo-Caldas Y;Clark A;Moroldo M;Robert C;Barrey E;López JM;Le Moyec L
马的耐力运动需要适应性过程，包括生理、生化和认知行为反应，以试图恢复稳态。我们假设，在马耐力运动过程中，血液代谢组，转录组和miRNome之间的关系的识别可以提供对耐力运动的分子反应的重要见解。出于这个原因，血清代谢组和全血转录组和miRNome数据从10匹马之前和之后的160公里耐力比赛。我们获得了基于11种独特代谢物、263种代谢基因和5种miRNA的全球调控网络，这些基因的表达在T1（耐力比赛后）相对于T0（基线，耐力比赛前）显著改变。该网络提供了对不同分子途径（例如能量和氧传感，氧化应激和炎症）之间的串扰的新见解，这些分子途径在单独分析单个代谢物或转录物时无法检测到。单一的代谢产物和转录本发挥多种作用，因此共享几个生化途径。使用调控影响因子度量分析，在转录因子和miRNA水平进一步证实了该调控网络。在31只独立动物的扩展队列中，多因素分析证实了乳酸、亚甲基衍生物、miR-21- 5 p、miR-16- 5 p、let-7家族和编码参与耐力比赛后主要与能量、泛素蛋白酶体和脂多糖免疫反应相关的代谢反应的蛋白质的基因之间的强关联。多因素分析还确定了T0时未能完成耐力比赛的可能性增加的潜在生物标志物。据我们所知，本研究是第一个提供代谢组，转录组和miRNome共调控网络的全面和综合概述，这些网络可能在调节马耐力运动的代谢和免疫反应中发挥关键作用。本文的在线版本（doi：10.1186/s12864-017-3571-3）包含补充材料，可供授权用户使用。
Endurance exercise in horses requires adaptive processes involving physiological, biochemical, and cognitive-behavioral responses in an attempt to regain homeostasis. We hypothesized that the identification of the relationships between blood metabolome, transcriptome, and miRNome during endurance exercise in horses could provide significant insights into the molecular response to endurance exercise. For this reason, the serum metabolome and whole-blood transcriptome and miRNome data were obtained from ten horses before and after a 160 km endurance competition. We obtained a global regulatory network based on 11 unique metabolites, 263 metabolic genes and 5 miRNAs whose expression was significantly altered at T1 (post- endurance competition) relative to T0 (baseline, pre-endurance competition). This network provided new insights into the cross talk between the distinct molecular pathways (e.g. energy and oxygen sensing, oxidative stress, and inflammation) that were not detectable when analyzing single metabolites or transcripts alone. Single metabolites and transcripts were carrying out multiple roles and thus sharing several biochemical pathways. Using a regulatory impact factor metric analysis, this regulatory network was further confirmed at the transcription factor and miRNA levels. In an extended cohort of 31 independent animals, multiple factor analysis confirmed the strong associations between lactate, methylene derivatives, miR-21-5p, miR-16-5p, let-7 family and genes that coded proteins involved in metabolic reactions primarily related to energy, ubiquitin proteasome and lipopolysaccharide immune responses after the endurance competition. Multiple factor analysis also identified potential biomarkers at T0 for an increased likelihood for failure to finish an endurance competition. To the best of our knowledge, the present study is the first to provide a comprehensive and integrated overview of the metabolome, transcriptome, and miRNome co-regulatory networks that may have a key role in regulating the metabolic and immune response to endurance exercise in horses. The online version of this article (doi:10.1186/s12864-017-3571-3) contains supplementary material, which is available to authorized users.