Abstract P205: Association of Angptl3/8 and 4/8 With Plasma Metabolites Before and After Exercise Training

Introduction: Angiopoietin like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of lipoprotein lipase and modifiable by regular exercise. However, the molecular underpinning of these novel biomarkers has not been fully elucidated. The purpose of this study was to examine the associations between plasma metabolites and ANGPTL3/8 and 4/8 before and after exercise training. Methods: Measurements were taken before and after 20 weeks of exercise training in 630 adults (36% Black, 56% women, mean age 35 yrs) of the HERITAGE Family Study. Meso Scale Discovery immunoassays were used to measure ANGPTL3/8 and 4/8 in serum. Plasma metabolites (n=300 named) were measured using LC-MS and the HILIC-pos method. Linear mixed models tested the association between metabolites and each trait at baseline and post-training with full covariate adjustment. Significance was set to FDR<0.05. Results: A total of 111 and 93 metabolites were significantly associated with ANGPTL3/8 at baseline or post-training, respectively ( Figure 1A ). A total of 69 metabolites were associated with ANGPTL3/8 at both time points, including ketone bodies, acylcarnitines, and DMGV, while 24 metabolites were only associated at post-training including citric acid, methionine, and glycine. A total of 89 and 40 metabolites were significantly associated with ANGPTL4/8 at baseline or post-training, respectively ( Figure 1B ). A total of 13 metabolites were associated with ANGPTL4/8 at both time points including glycine and lysophospholipids, whereas 27 metabolites were associated only at post-training including hydroxyproline, N-Lignoceroyl Taurine, and methylguanidine. Conclusions: We identified several plasma metabolites associated with ANGPTL3/8 and 4/8 before and after exercise training. Our findings indicate potential metabolic pathways related to the exercise responsiveness of ANGPTL3/8 and 4/8, including glucose-alanine cycle, urea cycle, and glycine and methionine metabolism.