Abstract 13353: Association of Plasma Metabolites With Inflammatory Markers CRP and GlycA and Their Responses to Exercise Training

Introduction. C-reactive protein (CRP) and GlycA are established biomarkers of inflammation. Regular exercise tends to decrease CRP and GlycA levels. However, the spectrum of molecules associated with the anti-inflammatory effects of regular exercise are less well understood. Hypothesis. We hypothesized that distinct metabolite signatures exist for both baseline levels and exercise responsiveness of CRP and GlycA. Methods. Measures were performed before and after 20 weeks of endurance exercise training in 652 Black and White adults from the HERITAGE Family Study. A total of 300 targeted plasma metabolites were measured using LC-MS. High-sensitivity CRP and GlycA were measured using automated assays and NMR spectroscopy (LabCorp), respectively. Linear mixed models were used to test: 1) Association of baseline metabolites with baseline hsCRP and GlycA and 2) Association of changes in metabolite with changes in hsCRP and GlycA. Models were adjusted for age, sex, race, BMI, with family membership as a random variable, with change models also adjusting for baseline trait value. Significance was determined as FDR<0.05. Results. Baseline levels and changes of hsCRP and GlycA were moderately correlated (r=0.51 and 0.31, p<0.0001 for both, respectively). At baseline, 40 and 94 metabolites were associated with hsCRP and GlycA, respectively, with 30 metabolites associated with both phenotypes. The top baseline associations for both traits included multiple species of lysophosphatidylcholine (LPC) and phosphatidylethanolamine (PE), while cortisol, biliverdin, and bilirubin were among the metabolites associated with GlycA only. The changes in only one metabolite were associated with concomitant changes in CRP, while no associations were found for change in GlycA. Conclusions. Plasma metabolite associations with baseline hsCRP overlapped with those associated with baseline GlycA levels. Several unique metabolite associations with baseline GlycA were identified, including molecules in established inflammatory pathways. Metabolite changes with exercise were not associated with changes in either measure. These findings have implications for the use of metabolites as signatures of systemic inflammation vs as targets of lifestyle interventions.