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Background: The mechanism for an abnormal pattern of triglyceride (TG) metabolism in response to a meal still needs further investigation. Extensive pieces of evidence have shown that apolipoprotein CIII (apoCIII) is a critical modulator of plasma TG metabolism mostly by inhibiting the hydrolysis of TG. Little is known about the role of apoCIII contained in high density lipoprotein (HDL) in plasma TG metabolism after a meal., Methods: Fasting and 4-hour postprandial peripheral venous blood were collected in 91 subjects selected from our hospital. Serum lipid parameters, apoCIII levels and HDL subcomponents were tested by standard laboratory procedures, ELISA, and nuclear magnetic resonance (NMR), respectively. The t-test, and Non-parametric tests were performed to examine differences between groups, Pearson's correlation and multiple regression analysis were used to assess the correlations between apoCIII (HDL-associated or nonHDL-associated) and postprandial TG., Results: There was a significant increase in TG after a meal compared to fasting status [155.40(96.70-251.07) mg/dl.vs.118.53(83.38-173.29)mg/dl, p < 0.001]. However, the total apoCIII levels were unchanged before (11.56(7.89-16.22) mg/dl) and after a meal (11.66(7.75-16.02)mg/dl, p = 0.124), while a significant increase in HDL-associated apoCIII (HDL-apoCIII) was observed from fasting (5.25(3.92-7.83)mg/dl) to post-meal (6.46(4.57-8.76)mg/dl, p = 0.001). Unlike nonHDL-apoCIII, HDL-apoCIII was positively correlated with both fasting and postprandial plasma TG in subjects with baseline plasma TG > 118.53 mg/dl (R = 0.503, p < 0.001 for fasting, R = 0.584, p < 0.001 for postprandial). Besides, in the subjects who had an abnormal TG response to a meal, which was defined as postprandial plasma TG increase of>30% compared to baseline TG levels, postprandial HDL-apoCIII was also increased significantly [5.37(3.52-7.02)mg/dl.vs.6.64(4.61-8.86)mg/dl, p = 0.001]. The enrichment of apoCIII in HDL led to changes of TG, cholesterol, free cholesterol, phospholipid and apoAII contents in HDL particles defined by NMR., Conclusion: Enrichment of apoCIII in HDL particles potentially plays an independent role in postprandial hypertriglyceridemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)