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Charles S. Schwartz1, Jacob L. Barber2,,1, Sujoy Ghosh3,,4, Anand Rohatgi5, Theodoros Kelesidis6, Claude Bouchard, FACSM4, Mark A. Sarzynski, FACSM1. 1University of South Carolina, Columbia, SC. 2Beth Israel Deaconess Medical Center, Boston, MA. 3Duke-National University of Singapore Medical School, Singapore. 4Pennington Biomedical Research Center, Baton Rouge, LA. 5University of Texas Southwestern Medical Center, Dallas, TX. 6University of California Los Angeles, Los Angeles, CA.

BACKGROUND: The functional properties of high-density lipoproteins (HDL), such as reduced antioxidant function that is linked to increased HDL lipid peroxidation (HDLox), may be more indicative of cardiovascular risk than HDL cholesterol (HDL-C) concentrations. Although exercise is well known to improve HDL-C, the effects of chronic exercise on HDLox are less understood. PURPOSE: To examine changes in HDLox in response to exercise training and how these changes relate to concomitant changes in other HDL-related traits. METHODS: HDLox was quantified in apoB-depleted serum before and after 20 weeks of endurance exercise training in 149 subjects (age 34.3±13.3 years, 60% female, 30% self-identified Black) from the HERITAGE Family study using the Amplex Red cholesterol assay (Invitrogen). A lower HDLox indicates improved HDL function. Exercise induced changes were calculated as the difference between post-training and baseline values. Exercise response was examined via paired t-tests in the total sample and stratified by sex. Partial correlations controlling for age, sex, and race were performed to investigate associations between HDLox and HDL traits in response to exercise training. RESULTS: HDLox significantly decreased following exercise training (mean -3.1%, standard error (SEM) 2.0, p=0.004). HDLox training response differed by sex (p=0.01), with females showing a significant decrease (-7.3%, SEM 2.6%, p=0.0006), whiles males exhibited no change (3.2%, SEM 3.0%, p=0.87). Exercise-induced changes in HDLox were inversely correlated with concomitant changes in HDL-C (r= -0.57, p<0.0001), apoA-I (r= -0.30, p<0.0001), and HDL-TG (r= -0.20, p=0.03). Additionally, changes in HDL particle size (r= -0.33, p=0.002) and the concentrations of total (r= -0.20, p=0.03), large (r= -0.27, p=0.002), and medium (r= -0.19, p=0.03) HDL particles were inversely correlated with change in HDLox. Change in small HDL particle concentration and cholesterol efflux capacity were not associated with change in HDLox. CONCLUSION: Endurance exercise training improved HDL function with respect to its anti-oxidative properties. Improvements in HDLox appear stronger in women and related to increases in HDL-C, HDL size, and the concentration of medium and large HDL subclasses. Further studies are needed to identify the mechanisms underlying sex differences, including differences in endogenous hormone levels.

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