Document Type

Article

Abstract

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. 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. 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's correlations at baseline and following exercise training (significance: P < 7.4 × 10−4). The effect of exercise training on HDL-SPE was examined using paired t-tests (significance: P < 0.05). Mean (SD) HDL-SPE was 1.40 (0.19) and higher in females compared with males and in White participants compared with Black participants. Baseline HDL-SPE was strongly associated with HDL-C (r = 0.45) and apoA-I (r = 0.43, both P < 6.9 × 10−24) 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 < 1.3 ×10−4). 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 coronary artery disease may experience the largest benefits from exercise training as related to this novel biomarker of HDL function.

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.jlr.2026.100993

Rights

© 2026 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

APA Citation

Leszczynski, E. C., Schwartz, C. S., Jacobs, K. J. C., Dev, P. K., Ghosh, S., Robbins, J. M., Gerszten, R. E., Rohatgi, A., Collier, T. S., Konrad, R. J., Sato, M., Zubirán, R., Bouchard, C., Neufeld, E. B., Remaley, A. T., & Sarzynski, M. A. (2026). Characterization and response to exercise training of HDL-specific phospholipid efflux. Journal of Lipid Research, 67(3), 100993.https://doi.org/10.1016/j.jlr.2026.100993

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