Montserrat de la Paz, SergioMartín Rubio, María EstherGrao Cruces, Elena2025-05-022025-05-022025-01-17Grao Cruces, E. (2025). High-density lipoprotein composition in metabolic syndrome and postprandial metabolism and its functional implications. (Tesis Doctoral Inédita). Universidad de Sevilla, Sevilla.https://hdl.handle.net/11441/172390High-density lipoproteins (HDLs) are complex blood circulating particles composed of lipids and proteins. They participate in blood lipid transport and are essential for cholesterol clearance from peripheral tissues, as HDLs are key players in reverse cholesterol transport, which is the reason why HDLs have been traditionally considered as "the good cholesterol". HDLs have been studied in terms of composition, functionality, and size. HDLs have more than 250 proteins and 300 lipids and show different functionalities beyond cholesterol transport. Therefore, evidence suggests that HDLs are more than cholesterol transporters, and their good functioning and metabolism are essential for their role in preventing CVD risk. The role of HDLs is critical in pathological conditions, such as metabolic syndrome (MetS), and in physiological processes, such as postprandial lipemia, two metabolic phenomena that are related to CVDs. MetS clusters together different CVD risk factors, including low HDL-C. HDLs in MetS have been described to have an impaired functionality and differential composition. Postprandial lipemia, which is the physiological process that occurs after the intake of a high-fat meal, is known to modify the HDL composition. However, little is known about the composition-function link of HDLs in MetS and the effects of different dietary fatty acids on the acute HDL lipid remodelling. Therefore, the aim of this thesis was to explore the HDL composition-function relationship in the framework of MetS and the effects of saturated and unsaturated dietary fatty acids on the HDL postprandial lipid remodelling. For the study of HDL biology in MetS, 15 MetS patients and 18 healthy controls participated, and we employed state-of-the-art liquid chromatography (LC) coupled with mass spectrometry (MS)-based proteomic and lipidomic analyses to study HDL composition, a cell-based assay to measure HDL cholesterol efflux capacity (CEC), and different bioinformatic tools to further characterise the HDL composition-function link. For the evaluation of the acute HDL lipid remodelling, a state-of-the-art LC-MS lipidomic analysis was employed to study the HDL and serum lipid composition. A crossover design, in which each subject was its own control, was followed. In four different days the four participants of the study were given a different meal, enriched in different dietary fatty acids. The protein and lipid composition of HDLs was altered in MetS patients compared to healthy volunteers, and these changes were closely associated with HDL functional impairment and key drivers of MetS. In postprandial lipemia, the HDL lipidome was highly remodelled and the dietary fatty acid composition of the meal produced significant differences in the HDL lipid remodelling. These results suggest that HDL compositional differences might lead to HDL dysfunction in MetS, and that HDl biology is tightly linked to various traits of MetS. Additionally, the differential HDL lipid remodelling observed in postprandial lipemia suggests strong effects of dietary fats on HDL biology, effects that might influence their functioning in postprandial metabolism and fasting state.application/pdf209 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/embargoedAccess