PB0136 - Excessive exercise increases metabolites associated with pathophysiologic changes in ultramarathon runners

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

Zofia Wicik, PhD

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland

Presenting Author(s)

Ceren Eyileten, DVM, PhD, MSc (she/her/hers)

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland

Co-Author(s)

MM

Mikołaj Marszałek

Student
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland
AC

Andrzej Ciechanowicz

Senior Researcher
Department of Regenerative Medicine Warsaw Medical University, Warsaw, Poland
Warsaw, Mazowieckie, Poland
PS

Piotr Szwed

Researcher
Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, 02-097 Warsaw, Poland
Warsaw, Mazowieckie, Poland
AN

Anna Nowak

PhD Candidate
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland; Doctoral School, Medical University of Warsaw, 02-091, Warsaw, Poland
Warsaw, Mazowieckie, Poland
�M

Łukasz Małek

Professor
Department of Epidemiology, Cardiovascular Disease Prevention, and Health Promotion, National Institute of Cardiology, Warsaw, Poland
Warsaw, Mazowieckie, Poland
SW

Szczepan Wiecha

Researcher
Department of Epidemiology, Cardiovascular Disease Prevention, and Health Promotion, National Institute of Cardiology, Warsaw, Poland
Warsaw, Mazowieckie, Poland
MP

Marek Potuła

Professor
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland

Background: Acute bouts of extreme physical activity trigger molecular responses reflected by changes in inflammation/metabolic pathways, yielding detrimental effects on the cardiovascular system (CVS). We assessed high-intensity and long-lasting exercise (100km run) on the metabolomic changes in of long term ultramarathon runners.

Aims: We aimed to assess the effects of high-intensity and long-lasting exercise prototype (100km run) on the metabolomic changes in a unique population of high-level long-term ultra-marathon runners.

Methods: Plasma samples were collected from ultramarathon runners (n=22) with 2-time points: before and after the run: Completion (100km) or exhaustion (median 74km). For untargeted metabolomic analysis we used ultra-high resolution Fourier-Transfor IonCyclotron ResonanceMassSpectrometry. Identified compounds were ontologically analyzed using MetaboAnalystR, MetscapeCytoscape plugin was used for metabolite-gene interaction analysis via Biomart and DisGeNet.

Results: Mann-Whitney test (FDR < 0.05) identified 1601 up and 1030 downregulated metabolites with at least a 2-fold difference after high-intensity run. Enrichment analysis showed that the top pathways affected by analyzed metabolites were the TCA cycle (FDR=0.0442), metabolism of; Sphingolipids (p=0.00774), Glyoxylate and dicarboxylate (p=0.0249) and Butanoate (p=0.0352). Top disease phenotypes associated with differentially regulated metabolites were critical illness (major trauma, severe septic shock, or cardiogenic shock)(p=0.00154) and multiple CVS-related diseases. Top after the run up-regulated metabolites identified in the study included heart failure associated acetylcarnitines2 CAR(14:2)(log2FC=11.57;AUC=0.97), Dodecanoylcarnitine(2.00;0.960), 9-Decenoylcarnitine(1.78;0.95), CAR(DC8:0)(14.99;0.94), but also 2-Carboxy-5,7-dimethyl-4-octanolide(8.04;0.98), Methylmalonic acid(9.33;0.96) and cardiotoxic Cyclophosphamide(16.29;0.940). Top downregulated metabolites after the run included potentially cardio-protective Gamma-Glutamylglutamic-acid (log2FC=-1.81;AUC=0.85), Fructose 1,6-bisphosphate(-2.42;0.88), Oleamide(-1.82;0.86) and gamma-Glutamylglycine(-7.98;0.85). Interaction network analysis focused on genes associated with CVS identified atherosclerosis/ obesity-related Phospholipase-A2-Group-IB(PLA2G1B) as potentially the most affected gene by analyzed metabolites.

Conclusion(s): Results show a 2-fold post run increase in metabolites that are both potential markers for acute exercise and that are strongly associated with CV diseases. This calls for consideration of the detrimental effects of excessive exercise and implementation of monitoring in amateur athletes.

Funding: ZW:Miniatura,NCN,Poland,2022/06/X/NZ7/01071;PS:Preludium,NCN,Poland,2021/41/N/NZ2/02783.