Exercise Training, Lipoprotein Subfractions, and Molecular Lipidomics: Mechanistic Insights into Atherogenic Risk Phenotypes—A Structured Narrative Review

Objective: Exercise modality exerts distinct effects on lipid metabolism, shaping both circulating lipid profiles and the distribution of lipoprotein subfractions. This structured narrative review assessed evidence on how aerobic training, resistance exercise, high-intensity interval training (HIIT), and subsequent detraining modulate conventional plasma lipids, lipoprotein subfraction distribution, and molecular lipidomic signatures across diverse populations, with a focus on adaptation kinetics and on changes in lipid profiles after training cessation. Methods: We conducted a structured narrative review based on a targeted literature search of PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar from database inception through 31 December 2025. Primary human exercise studies (randomized and non-randomized controlled trials, acute crossover or pre–post experiments, and detraining studies) reporting conventional lipids, lipoprotein subfractions, HDL function, or molecular lipidomic outcomes were synthesized; systematic reviews and meta-analyses were used only as contextual evidence. Results and Conclusions: Aerobic training frequently shifts lipoprotein subfraction distribution toward larger LDL particles and fewer small dense LDL (sd-LDL) particles, whereas its effect on circulating HDL-C concentration is variable and depends on baseline metabolic phenotype and training volume. HDL-C concentration does not necessarily reflect changes in HDL subclass distribution, composition, or directly measured function (e.g., cholesterol efflux capacity). Meta-analytic evidence indicates that HIIT is not superior to moderate-intensity continuous training (MICT) for most blood lipid outcomes, apart from a modest advantage for HDL-C. Favorable subfraction changes have been observed after interventions as short as four weeks, although this does not establish a minimum effective duration. Detraining data, largely restricted to conventional lipids, indicate that total cholesterol and LDL-C can deteriorate within weeks of training cessation, whereas subfraction- and lipidomic-level detraining responses remain largely unstudied. Untargeted lipidomic studies suggest that exercise-only training can reduce saturated and monounsaturated species across sphingolipid, glycerolipid, and glycerophospholipid classes, whereas in a factorial diet–exercise trial most lipidomic changes were attributable to diet. Current data are insufficient to establish a superiority of evening over morning exercise. Because the available literature assesses intermediate circulating biomarkers rather than plaque dynamics or clinical cardiovascular events, the findings indicate modification of atherogenic risk phenotypes rather than proven atherosclerosis prevention.