Duez Hélène, Lamarche Benoît, Valéro René, Pavlic Mirjana, Proctor Spencer, Xiao Changting, Szeto Linda, Patterson Bruce W, Lewis Gary F
Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Canada.
Circulation. 2008 May 6;117(18):2369-76. doi: 10.1161/CIRCULATIONAHA.107.739888. Epub 2008 Apr 28.
Hepatic lipoprotein production has been shown previously to be regulated by free fatty acid (FFA) flux to the liver, whereas intestinal lipoprotein production is stimulated mainly by ingested fat absorbed from the intestinal lumen. Emerging evidence indicates that intestinal lipoprotein production is increased in insulin resistance and type 2 diabetes mellitus, conditions that are associated with increased levels of circulating FFAs. Here we investigated whether short-term elevation of plasma FFAs stimulates intestinal apolipoprotein (apo) B-48- and hepatic apoB-100-containing triglyceride-rich lipoprotein (TRL) production in humans in the fed state.
TRL apoB-48 and apoB-100 metabolism were examined in 12 healthy men during a constant fed state. The studies were as follows, respectively: (1) Intralipid/heparin was infused intravenously immediately before and during the kinetics study to induce an approximately 3-fold difference in plasma FFA compared with the saline study; (2) saline was infused intravenously as a control. ApoB-48- and apoB-100-containing TRL production and clearance were determined with a 12-hour primed constant infusion of [D3]L-leucine and multicompartmental kinetic modeling. TRL apoB-48 production rate was 69% higher in the Intralipid/heparin study than in the saline control (5.95+/-1.13 versus 3.53+/-0.58 mg/kg per day; P=0.027), and there was no significant difference in TRL apoB-48 clearance. TRL apoB-100 concentrations were also increased (P<0.001) and TRL apoB-100 production rate was 35% higher in the Intralipid/heparin study compared with saline (28+/-4 versus 21+/-3 mg/kg per day; P=0.020).
This is the first study to demonstrate that intestinal TRL apoB-48 production is increased after short-term elevation of plasma FFAs in humans in the fed state, similar to the well-described stimulation of hepatic TRL apoB100-containing particles by FFAs.
先前的研究表明，肝脏脂蛋白的产生受肝脏游离脂肪酸（FFA）通量的调节，而肠道脂蛋白的产生主要受从肠腔吸收的摄入脂肪的刺激。新出现的证据表明，在胰岛素抵抗和2型糖尿病中，肠道脂蛋白的产生会增加，这些情况与循环FFA水平升高有关。在此，我们研究了在进食状态下，血浆FFA的短期升高是否会刺激人体肠道载脂蛋白（apo）B - 48和肝脏含apoB - 100的富含甘油三酯脂蛋白（TRL）的产生。
在12名健康男性处于持续进食状态时，检测TRL apoB - 48和apoB - 100的代谢情况。研究分别如下：（1）在动力学研究前及研究过程中静脉输注脂肪乳/肝素，以使血浆FFA与生理盐水研究相比产生约3倍的差异；（2）静脉输注生理盐水作为对照。通过12小时的[D3]L - 亮氨酸预充持续输注和多室动力学模型来测定含apoB - 48和apoB - 100的TRL的产生和清除情况。脂肪乳/肝素研究中TRL apoB - 48的产生率比生理盐水对照组高69%（分别为5.95±1.13与3.53±0.58毫克/千克/天；P = 0.027），并且TRL apoB - 48清除率无显著差异。与生理盐水相比，脂肪乳/肝素研究中TRL apoB - 100浓度也升高（P < 0.001），且TRL apoB - 100产生率高35%（分别为28±4与21±3毫克/千克/天；P = 0.020）。
这是第一项证明在进食状态下人体血浆FFA短期升高后肠道TRL apoB - 48产生增加的研究，类似于FFA对肝脏含TRL apoB100颗粒的明确刺激作用。
