CRNH-O Mass Spectrometry Core Facility, Nantes, France.
NUN, INRA, CHU Nantes, UMR 1280, PhAN, IMAD, CRNH-O, IRS-UN-Spectrométrie de Masse-8, quai Moncousu, 44000, Nantes, France.
Sci Rep. 2020 Sep 24;10(1):15585. doi: 10.1038/s41598-020-72323-w.
The aim of this study was to compare the kinetics of apolipoprotein (apo)A-I during fed and fasted states in humans, and to determine to what extent the intestine contributes to apoA-I production. A stable isotope study was conducted to determine the kinetics of apoA-I in preβ high-density lipoprotein (HDL) and α-HDL. Six healthy male subjects received a constant intravenous infusion of H-leucine for 14 h. Subjects in the fed group also received small hourly meals. Blood samples were collected hourly during tracer infusion and then daily for 4 days. Tracer enrichments were measured by mass spectrometry and then fitted to a compartmental model using asymptotic plateau of very-low-density lipoprotein (VLDL) apoB100 and triglyceride-rich lipoprotein (TRL) apoB48 as estimates of hepatic and intestinal precursor pools, respectively. The clearance rate of preβ-HDL-apoA-I was lower in fed individuals compared with fasted subjects (p < 0.05). No other differences in apoA-I production or clearance rates were observed between the groups. No significant correlation was observed between plasma apoC-III concentrations and apoA-I kinetic data. In contrast, HDL-apoC-III was inversely correlated with the conversion of α-HDL to preβ-HDL. Total apoA-I synthesis was not significantly increased in fed subjects. Hepatic production was not significantly different between the fed group (17.17 ± 2.75 mg/kg/day) and the fasted group (18.67 ± 1.69 mg/kg/day). Increase in intestinal apoA-I secretion in fed subjects was 2.20 ± 0.61 mg/kg/day. The HDL-apoA-I kinetics were similar in the fasted and fed groups, with 13% of the total apoA-I originating from the intestine with feeding.
本研究旨在比较人体在进食和禁食状态下载脂蛋白（apo）A-I 的动力学，并确定肠道在多大程度上参与 apoA-I 的产生。采用稳定同位素研究来确定前β高密度脂蛋白（HDL）和α-HDL 中 apoA-I 的动力学。6 名健康男性受试者接受 H-亮氨酸恒速静脉输注 14 小时。进食组受试者还接受小时间歇性进餐。在示踪剂输注期间每小时采集血液样本，然后在接下来的 4 天每天采集一次。通过质谱法测量示踪剂丰度，然后使用渐近平台法拟合房室模型，将极低密度脂蛋白（VLDL）apoB100 和富含甘油三酯的脂蛋白（TRL）apoB48 分别作为肝前体池和肠前体池的估计值。与禁食受试者相比，进食个体的前β-HDL-apoA-I 清除率较低（p < 0.05）。两组之间在 apoA-I 产生或清除率方面没有观察到其他差异。血浆 apoC-III 浓度与 apoA-I 动力学数据之间未观察到显著相关性。相反，HDL-apoC-III 与 α-HDL 向 preβ-HDL 的转化呈负相关。进食组受试者总 apoA-I 合成没有显著增加。进食组（17.17 ± 2.75 mg/kg/天）和禁食组（18.67 ± 1.69 mg/kg/天）之间肝合成没有显著差异。进食组肠道 apoA-I 分泌增加 2.20 ± 0.61 mg/kg/天。禁食和进食组的 HDL-apoA-I 动力学相似，其中 13%的总 apoA-I 来自肠道。
