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Elsevier BV Journal of Biological Chemistry 300(3)
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    초록·키워드

    The bioactive components of human milk play a crucial role in its positive impact on newborn development. Extracellular vesicles (EVs) are small, membrane-enclosed, non-replicating vehicles secreted by lactocytes that may be important in newborn nutrition. The functions and dietary bioavailability of EVs may depend on their lipid composition. Oxylipins are polyunsaturated fatty acids (PUFA) derived metabolites present in EVs that may influence EV bioavailability by modulating the permeability of biological barriers, like the intestine. Objective. This research aims to characterize the PUFA derived metabolite content of human milk EVs. Methods. Mature human milk (n = 20) was obtained from Prolacta Bioscience (City of Industry, CA). EVs were isolated from human milk using differential centrifugation and concentrated using a precipitation reagent. Lipids were extracted from EVs and human milk using methanol and hexane, and then subjected to solid phase extraction to recover free oxylipins. Liquid chromatography-mass spectrometry was used to identify oxylipins and the oxylipins were quantified with internal standards. The relative amounts of oxylipins were computed and descriptive statistics were determined using Wilcoxon test for non normal distribution. Results. The EV isolation was characterized in accordance with guidance from the Minimal Information for the Study of EVs. Relative to total oxylipin content, the relative amounts of oxylipins derived from arachidonic acid (AA), linoleic acid (LA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) in EVs were 8.7%, 88%, 2.7%, and 0.18%, respectively. In whole human milk, the relative amounts of oxylipins derived from AA, LA, DHA, and EPA were 12%, 82%, 5.4%, and 0.89%, respectively. AA derived oxylipin content was decreased ∼25% (p = 0.002) in EVs compared to whole human milk. DHA derived oxylipin content in EVs was ∼50% lower (p < 0.001), and EPA derived oxylipin content was decreased ∼80% relative to whole human milk (p < 0.001). The relative amount of oxylipins derived from omega-6 fatty acids was greater than the relative amount of oxylipins from omega-3 fatty acids in EVs and in human milk. In EVs, 2.9% of total oxylipins were derived from omega-3 fatty acids compared to 6.3% in whole human milk (p < 0.001). In EVs, 97% of oxylipins were derived from omega-6 fatty acids compared to 93.7% in whole human milk (p < 0.001). Conclusions. The free oxylipin content of EVs differs between EVs and whole human milk. This finding may suggest selective partitioning or non-stochastic distribution of oxylipins in milk and milk derived EVs from lactocytes. The prominent increase in total omega-6 derived oxylipins in EVs suggests their importance in the bioavailability of dietary EVs. The study was funded by the USDA (2021-38420-34941 and 2020-67018-33315).

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