Moderate-intensity exercise training uniquely modulates circulating lipid species beyond classical lipid levels in humans

Background: Regular physical exercise shows significant health-related benefits, potentially through the modulation of lipid metabolism in an intensity-dependent manner. Methods: In this study, we profiled 794 plasma lipid species across 18 subclasses following a 24-week supervised concurrent and randomised exercise intervention at moderate and vigorous intensities in 101 young, sedentary adults. Findings: Here, we demonstrate that moderate-intensity exercise, but not vigorous-intensity, significantly increased plasma levels of glycerophospholipids and triacylglycerol species. Interestingly, we also identified a sex-specific response to moderate-intensity exercise, with men exhibiting elevated glycerophospholipids and lysophospholipids species, and women showing significant increases in triacylglycerols species. Increments in glycerophospholipids species were associated with improvements in cardiorespiratory fitness, i.e., VO₂peak. Interpretation: Importantly, while traditional lipid markers, including total cholesterol or triglycerides remained unchanged after the exercise intervention, our findings suggest that exercise partially exerts its health benefits by selectively targeting and modifying specific lipid subtypes in an intensity, sex-dependent manner. Funding: The study was supported by the Junta de Andalucía, Consejería de Transformación Económica, Industria, Conocimiento y Universidades Dirección General de Investigación y Transferencia del Conocimiento (ref. P18-RT-4455, ref. SOMM17/6107/UGR, and DOC 01151) and European Regional Development Funds (ERDF), the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), and PTA-12264, Retos de la Sociedad (DEP2016-79512-R), the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016 Excellence actions: Unit of Excellence on Exercise and Health (UCEES).