4. Discussion
CVD
It is well known that certain constituents of the diet directly affect the composition and structure of HDL and increase its vasoprotective and anti-inflammatory properties [Regarding our first finding, it was recently demonstrated that certain classes of lipids are more sensitive markers of dietary changes (PCs, TAGs and CEs) [In addition, the effect of the treatment was more evident in various lipids containing ω3 fatty acids. A significant increase in lipids containing DHA (e.g., PC-DHA, PC 15:0/22:6, PC 16:0/22:6, PC 18:0/22:6, TAG 58:8 and CE 22:6) was evidenced after 4 weeks in the ω3 milk group. Additionally, lipids esterified with EPA were also positively affected (e.g., PC 16:0/20:5, PC 38:5, PE 20:5/16:0, TAG 56:8 and CE 20:5). This is directly related to the fact that this group was supplemented with milk containing 150 mg EPA + DHA/100 mL of milk (daily intake of 375 mg). Our observations are also relevant since metabolites such as PC and TAG that contain PUFAs, particularly EPA, DHA and docosapentaenoic acid, showed inverse associations with CVD [The alterations in HDL metabolism were further corroborated by the enzymatic activity (related to lipid metabolism). PC is synthesized primarily by the cytidine diphosphate (CDP)-choline pathway or via phosphatidylethanolamine-N-methyltransferase (PEMT) activity [The beneficial effect of ω3 intake on HDL particles could also explain the fact that some lipids esterified with arachidonic acid (AA) showed decreases after intervention (PC 17:0/20:4, PC 20:3/20:4, PC O-18:0/20:4, PE 16:0/20:4, PE 18:0/20:4 and PI 16:0/20:4). This is highly relevant since it has previously been proposed that an increase in the EPA-to-AA ratio in HDLs is indicative of a more anti-inflammatory profile of HDL [Regarding the second finding, to date, sex-related differences in circulating lipids at molecular lipid species levels have been observed [Together with the fact that the type of supplementation produces profound changes in the HDL lipid profile, our third finding to highlight is that lipid changes are the result of a chain reaction. According to our network, lipid species changes occur in a coordinated fashion involving various members of the same or distinct lipid families. These relationships were previously exposed in an HDL lipidomic study with hypercholesterolemic pigs [A limitation of our study is the sample size (