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http://hdl.handle.net/10609/70664
Title: Understanding the response to endurance exercise using a systems biology approach: Combining blood metabolomics, transcriptomics and miRNomics in horses
Author: Mach Casellas, Núria
Ramayo Caldas, Yuliaxis
Clark, Allison
Moroldo, Marco
Robert, Céline
Barrey, Eric
López Martí, Jesús María
Le Moyec, Laurence
Keywords: endurance exercise
horses
metabolome
miRNome
multiple factor analysis
regulome
transcriptome
systems biology
Issue Date: Feb-2017
Publisher: BMC Genomics
Citation: Mach Casellas, N., Ramayo-Caldas, Y., Clark, A., Moroldo, M., Robert, C., Barrey, E., López Martí, J.M. & Le Moyec, L. (2017). "Understanding the response to endurance exercise using a systems biology approach: Combining blood metabolomics, transcriptomics and miRNomics in horses". BMC Genomics, 18. ISSN 1471-2164. doi: 10.1186/s12864-017-3571-3
Abstract: 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.
Language: English
URI: http://hdl.handle.net/10609/70664
ISSN: 1471-2164MIAR
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