Author(s): NEYROUD, D., DAUCOURT, C., PRIMAVESI, J., TAGLIAPIETRA, G., MOUFID TRAMBATY, T., CONEDERA, L., JAKOB, K., POCHON, J., GOSS, N., GALLART-AYALA, H., RINKER, J., GOTTARDO, R., IVANISEVIC, J., BAGGISH, A.L., Institution: UNIVERSITY OF LAUSANNE, Country: SWITZERLAND, Abstract-ID: 2190

INTRODUCTION:
The numerous health benefits of regular physical activity are well established. However, the molecular mechanisms underlying salutary impacts of exercise remain incompletely understood. In addition, the relationship between the exercise dose, defined by the product of exercise intensity and duration, and molecular responses to acute bouts of exercise remain largely unexplored. To address these knowledge gaps, the Human Exersome Initiative (HEI) is working to generate a comprehensive exercise-dose roadmap of the systemic biochemical response to exercise in humans. Here, we report the first results from the HEI, focusing on exercise-induced changes in the plasma lipidome.
METHODS:
Young healthy sedentary individuals [9 women, 24 ± 7 years, peak oxygen uptake (VO2-PEAK) = 42 ± 8 ml/kg/min] underwent maximal effort-limited cardiopulmonary exercise test to determine VO2-PEAK and the first ventilatory threshold (VT1). Subsequently, each participant performed 4 exercise sessions designed to isolate intensity (workloads corresponding with VT1−30%, VT1−15%, VT1, and VT1+15%; fixed duration = 30 min) and 4 sessions designed to isolate duration (10, 20, 30 and 60 min; fixed intensity = VT1−15%). All sessions were conducted after an overnight fast and were separated by ≥72 h. Blood plasma samples were collected pre-exercise, immediately post-exercise, and after 1 h of recovery for high-coverage targeted LC–MS/MS lipidomic profiling encompassing glycerolipids, glycerophospholipids, sphingolipids and fatty acyls (>2100 species assayed). Lipids were defined as “exercise responsive” based on limma analyses (FDR < 0.05).
RESULTS:
Among 673 precisely measured, annotated lipid, 387 (58%) were “exercise responsive”, with predominant lipid accumulation immediately after exercise (148 accumulated vs. 99 depleted), and predominant lipid depletion 60 min later (43 accumulated vs. 228 depleted). While significant changes in lipids were observed in response to all exercise sessions, the number of “responsive” lipids increased in parallel with both increasing exercise intensity and duration. Increasing intensity associated with a net increase in plasma lipid concentrations driven by fatty acids, ceramides, phosphatidylcholines and sphingomyelins. In contrast, increasing duration associated with a net decrease in plasma lipid concentrations driven predominantly by triacylglycerides. At 60 min post-exercise, net lipid concentration depletion, driven largely by triacylglycerides, was observed in response to both increases in exercise intensity and duration.
CONCLUSION:
These findings begin to clarify the response of the circulating plasma lipidome in response to acute bouts of exercise spanning clinically relevant exercise doses. Ongoing work will enable precise tailoring of exercise dose, for use in individualized exercise prescriptions and interventional studies, to target specific biologically and clinically relevant lipid species.