Abstract P201: Plasma Proteomic Signatures of Angptl3/8 and 4/8 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 biomarkers related to their exercise responses have not been fully elucidated. The purpose of this study was to examine the associations between plasma proteins 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 ANGPTL4/8 complexes in serum. Plasma proteins (n=4979 aptamers) were quantified using SomaScan. Linear mixed models tested the association between plasma proteins and each trait at baseline and post- training with full covariate adjustment. Significance was set to FDR<0.05. Results: A total of 862 and 126 proteins were significantly associated with ANGPTL3/8 at baseline or post-training, respectively, with 80 proteins associated at both time points, including PCSK9 and PLTP ( Figure 1A ). Conversely, 46 proteins were only associated with ANGPTL3/8 at post-training, 23 of which whose levels significantly changed with training including NRP1, ghrelin, HHIP, and APOA1. A total of 433 and 71 proteins were significantly associated with ANGPTL4/8 at baseline or post-training, respectively, with 46 proteins associated with both time points ( Figure 1B ). A total of 25 proteins were only associated with ANGPTL4/8 at post-training, 12 of which whose levels significantly changed with training including ghrelin, COL6A2, and MMP16. Conclusions: We identified a subset of proteins uniquely associated with exercise-induced changes in ANGPTL3/8 and 4/8. Thus, the responsiveness of ANGPTL3/8 and 4/8 to regular exercise may be related to cholesterol esterification, lipoprotein remodeling, inflammatory response, and regulation of fibrinolysis and coagulation among other biological pathways.