Cancer Diagnosis Program | Biorepositories and Biospecimen Research Branch

Search BRD Papers

Circulating miRNA Signaling for Fatty Acid Metabolism in Response to a Maximum Endurance Test in Elite Long-Distance Runners.

Author(s): Paulucio D, Ramirez-Sanchez C, Velasque R, Xavier R, Monnerat G, Dill A, Silveira J, Andrade GM, Meirelles F, Dornelas-Ribeiro M, Kirchner B, Pfaffl MW, Pompeu F, Santos CGM

Publication: Genes (Basel), 2024, Vol. 15, Page

PubMed ID: 39202447 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   This study investigated the effects of an endurance test on the plasma cell-free miRNA (cfmiRNA) profile of elite endurance athletes whose maximal oxygen uptake (VO2max) was in lowest (LVO2) or highest (HVO2) tertile.  The authors also investigated if volunteers in the LVO2 versus HVO2 group differed in terms of age, weight, height, fat percentage, weekly training distance, training experience or number of International Association of Athletics Federations (IAAF) points. K₂EDTA blood was collected from six male elite endurance athletes (long-distance runners, ≥100 km/week) after an 8 h fast and again after eating a standardized meal (a slice of bread, a banana and water) and a graded endurance test on a treadmill. The athletes were chosen based on having a VO2max in the lowest or highest tertile of twenty-three athletes during the endurance test. VO2max was determined based on the following a) oxygen consumption (VO2) plateau ≤ 150 mL/min; b) respiratory exchange ratio of carbon dioxide production (VCO2) to VO2 ≥1.10; c) peak heart rate at ≥90% of the age-predicted peak; and d) rating of perceived exertion on the Borg scale of ≥19 in the last 10 sec of each phase of the test. Plasma was separated from blood by centrifugation at 3000 g for 12 min and stored at -80°C. RNA was extracted from plasma using the miRNeasy Serum/Plasma Kit and quantified by spectrophotometry. Levels of 1113 miRNAs were profiled using the real-time PCR based miRNome miRNA Profiling Kit. Expression was normalized using the geometric mean of the ten most stably expressed miRNAs and then each miRNA was then normalized to the specimen with the lowest expression of that miRNA. Differentially expressed miRNAs were identified between groups using a two-tailed paired t-test and among the four groups using ANOVA with the Benjamini–Hochberg correction for multiple testing. Core pathways were identified using the top 20 most affected miRNA for each comparison using mirPath (v.3.0) and Tarbase v7.0 from the DIANA tools. The pathways identified were merged using the EASE score modification of Fisher’s exact test for hypergeometric distribution with false discovery rate (FDR) correction.

   Summary of Findings:

   The mean VO2max was significantly higher in the HVO2 than LVO2 group (75.4 mL/kg min versus 60.1 mL/kg min, P=0.007). Principal component analysis (PCA) based on the profile of differentially expressed miRNA clustered the specimens based on if they were collected before or after the endurance test.  Similarly, when specimens from the HVO2 and LVO2 groups were analyzed separately, the specimens clustered based on if they were collected before or after the endurance test. PCA of specimens from either pre- or post- endurance test clustered specimens from HVO2 and LVO2 patients separately.  When the top 20 most differentially expressed miRNA from each comparison (HVO2 pre- versus post-endurance test, LVO2 pre- versus post-endurance test, HVO2 versus LVO2 pre-endurance test and HVO2 versus LVO2 post-endurance test) were compared, none were significant in all comparisons. However, 8 miRNAs were shared between the HVO2 pre- versus post-endurance test and LVO2 pre- versus post-endurance test groups; no miRNAs were common between the HVO2 versus LVO2 pre-endurance test and HVO2 versus LVO2 post-endurance test groups. Further analysis of the top 20 miRNAs differentially expressed in each comparison found 9 pathways for the pre- versus post- endurance test comparison, 10 pathways for the LVO2 pre- versus post-endurance test comparison and 13 pathways for the HVO2 pre- versus post-endurance test comparison. Fatty acid biosynthesis was found to be significant in all comparisons and fatty acid metabolism was significant in the comparison between pre-versus post-endurance test for the entire group and the LVO2 group and for HVO2 versus LVO2 post-endurance test. Additional pathways identified in one or more comparison included the ECM receptor, lysine degradation, Hippo signaling, and TGF-β pathways. The average age, weight, height, fat percentage, weekly training distance, training experience and number of International Association of Athletics Federations (IAAF) points were comparable between patients from the LVO2 and HVO2 groups.

   Biospecimens

   • Bodily Fluid - Plasma
   • Bodily Fluid - Blood

   Preservative Types

   • Frozen

   Diagnoses:

   • Normal

   Platform:

   Analyte	Technology Platform
   RNA	Low density array
   RNA	Real-time qRT-PCR

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Acquisition	Time of biospecimen collection	Pre-endurance test Post-endurance test
   Preaquisition	Diagnosis/ patient condition	VO2max in lowest tertile (LVO2) VO2max in highest tertile (HVO2)

   View more