Abstract 423: Ultramarathon Induces Metabolite Changes Associated With Pathophysiology Of Cardiovascular Diseases- In Silico And In Vivo Analysis

Abstract

Regular physical exercise increase longevity, however acute intensive/longterm exercise can trigger the CV pathophysiological processes. Ultramarathon runners' plasma (n=22) with 2time points: before and after the run: Completion (100km) or exhaustion (median74km) was used for analysis. For untargeted metabolomic analysis; ultrahigh resolution MassSpectrometry with electrospray ion source in direct injection used and analyzed by T-Rex2D algorithm. Identified compounds analyzed using MetaboAnalystR/MetscapeCytoscape plugin was used for metabolite-gene interaction analysis, identifying 1601 up and 1030 downregulated metabolites with min 2 fold difference after ultramarathon run Enrichment analysis showed that TCA cycle (FDR=0.0442), metabolism of; Sphingolipids (p=0.008), Glyoxylate and dicarboxylate (p=0.03) and Butanoate (p=0.04) were the top metabolites. After the run top upregulated metabolites were related to heart failure associated metabolites; acetylcarnitines2 CAR(14:2) (AUC=0.97) Dodecanoylcarnitine (2.00;0.960), 9-Decenoylcarnitine (1.78;0.95), CAR(DC8:0) (14.99;0.94), 2Carboxy5,7dimethyl4octanolide (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 cardioprotective Gamma Glutamylglutamic acid (log2FC=-1.81;AUC=0.85), Fructose 1,6bisphosphate (-2.42;0.88)4, Oleamide (-1.82;0.86) and gammaGlutamylglycine (-7.98;0.85).Interaction network analysis showed genes associated with atherosclerosis/obesity-related PhospholipaseA2,IB (PLA2G1B) as potentially the most affected gene by analyzed metabolites. Twofold post run increase in metabolites showed they are both potential markers for acute exercise and are strongly associated with CV diseases. This calls for consideration of the detrimental effects of excessive exercise and implementation of monitoring in amateur athletes.