Medicine

Eric C. Leszczynski, Charles S. Schwartz, Kiani Jacobs, Prasun K. Dev, Sujoy Ghosh, Jeremy M. Robbins, R. Gerszten, A. Rohatgi, Timothy S. Collier, R. Konrad, M. Sato, R. Zubirán, Claude Bouchard, E. Neufeld, Alan T Remaley, M. Sarzynski

2026.2.1JOURNAL OF LIPID RESEARCH

DOI: 10.1016/j.jlr.2026.100993

Abstract

INTRODUCTION The HDL-specific phospholipid efflux (HDL-SPE) assay is a novel cell-free measure of HDL function that is inversely associated with coronary artery disease (CAD). However, the effect of exercise training on HDL-SPE is unknown. The purpose of this study was to examine the effect of exercise training on HDL-SPE in a large, diverse cohort free of overt disease.

METHODS Clinical and functional measures of HDL were taken before and after 20 weeks of endurance exercise training in 508 participants from the HERITAGE Family Study. Associations of HDL-SPE with HDL-related traits were examined using Pearson correlations at baseline and following exercise training (significance: p<7.4x10-4). The effect of exercise training on HDL-SPE was examined using paired t-tests (significance: p<0.05).

RESULTS Mean (SD) HDL-SPE was 1.40 (0.19) and higher in females compared to males and in White participants compared to Black participants. Baseline HDL-SPE was strongly associated with HDL-C (r=0.45) and apoA-I (r=0.43, both p<6.9x10-24), but not with measures of cholesterol efflux. Mean HDL-SPE increased (0.023, p=0.002) following exercise training, but these increases only occurred in those with the lowest baseline HDL-SPE levels. Change in HDL-SPE was associated with changes in HDL-C (r=0.27), medium HDL concentration (r=0.24), and apoA-I and HDL size (r=0.17, all p<1.3x10-4).

CONCLUSION HDL-SPE increased following regular exercise and changes in HDL-SPE were related to changes in HDL size and subclass concentrations. Our findings demonstrate that individuals at higher risk for CAD may experience the largest benefits from exercise training as related to this novel biomarker of HDL function.

Citation format

LESZCZYNSKI, Eric C., et al. Characterization and response to exercise training of high-density lipoprotein-specific phospholipid efflux. JOURNAL OF LIPID RESEARCH, 2026, 67(3): 100993.