Abstract 504: Association of Exercise-Induced Changes in Cholesterol Efflux Capacity with Changes in the HDL Proteome

Background: HDL function has recently been identified as a strong predictor of cardiovascular risk. Exercise is well known to effect HDL metabolism and cardiovascular disease risk, however the effects of exercise on measures of HDL function and composition are less well known. Methods: We examined changes in cholesterol efflux capacity and concomitant changes in the HDL proteome and lipolytic enzymes in 19 white, non-related, individuals from the HERITAGE Family Study. Measurement of the efflux of radiolabeled and BODIPY-labeled cholesterol from J774 macrophages to apoB depleted plasma, along with untargeted HDL proteome profiling and post-heparin hepatic and lipoprotein lipase activities, was performed at baseline and following a 20-week endurance exercise program. Results: There was no effect of regular exercise on cholesterol efflux capacity, but a wide variation in response to exercise was observed (range: -0.28 to 0.40 normalized efflux). Changes in hepatic lipase and lipoprotein lipase activities were moderately positively correlated with changes in radiolabeled ABCA1 and negatively correlated with changes in non-ABCA1 efflux ( Table 1 ). A total of 33 known HDL proteins were identified in all 19 subjects. Only changes in albumin and APOE abundance were nominally (p<0.05) correlated with changes in BODIPY-labeled cholesterol efflux, whereas IGHA1, IGHG2, C6, and SAA4 levels were correlated with global radiolabeled cholesterol efflux ( Table 1 ). Discussion: This pilot study provides limited evidence for a potential role of lipolytic enzymes and select HDL proteins as mediators of changes in cholesterol efflux capacity in response to regular exercise. Future studies with larger sample sizes are needed to further examine how alterations in the HDL proteome are related to HDL function.