EXERCISE TRAINING-INDUCED CHANGES IN LIPID TRAITS ARE ASSOCIATED WITH CHANGES IN CIRCULATING PROTEINS AND METABOLITES

PURPOSE: To examine the molecular mechanisms underlying beneficial effects of regular exercise on lipid metabolism. METHODS: Circulating proteins (n = 4979), metabolites (n = 300), and lipids/lipoproteins were measured in 647 Black and White adults from the HERITAGE Family Study at baseline and after 20 weeks of supervised endurance training. The current analysis focused on 7 lipid/lipoprotein traits that significantly changed with training: HDL- cholesterol (HDL-C), triglycerides (TG), large TG-rich lipoprotein particles (LTRLP), large HDL particles (LHDLP), small LDL particles (SLDLP), and mean TRLP (TRLPz) and LDLP size (LDLPz). The relationship between exercise-induced fold changes in circulating molecules and changes in lipid traits was examined using sparse canonical correlation analysis, which tests the joint associations between two sets of variables by creating composite canonical variates. All variables were corrected for age, sex, race, BMI, baseline value, and family membership via linear mixed models. RESULTS: We identified 3 canonical variate pairs of exercise-induced changes in lipid traits and circulating molecules. Molecular variate 1 was positively correlated with changes in TG, LTRLP, SLDLP, and TRLPz (r = 0.29-0.57, p < 0.0001). Conversely, molecular variate 3 was negatively correlated with changes in TG, LTRLP, SLDLP, and TRLPz (r = -0.30 to -0.39, p < 0.0001), and positively correlated with changes in LDLPz (r = 0.38, p < 0.0001). Molecular variate 2 was negatively correlated with HDL-C (r = -0.46, p < 0.0001) and LHDLP (r = -0.22, p < 0.0001) changes with training. Molecular loadings on the respective variates were largely distinct (Table 1). CONCLUSIONS: We identified groups of circulating molecules whose changes in response to exercise training are associated with changes in the plasma lipid and lipoprotein profile and may provide insights into the mechanisms underlying exercise-induced changes in lipid metabolism.