Jong M C, van Ree J H, Dahlmans V E, Frants R R, Hofker M H, Havekes L M
TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands.
Biochem J. 1997 Jan 15;321 ( Pt 2)(Pt 2):445-50. doi: 10.1042/bj3210445.
The function of apolipoprotein (apo) C1 in vivo is not clearly defined. Because transgenic mice overexpressing human apoC1 show elevated triacylglycerol (TG) levels [Simonet, Bucay, Pitas, Lauer and Taylor (1991) J. Biol. Chem. 266, 8651-8654], an as yet unknown role for apoC1 in TG metabolism has been suggested. Here we investigated directly the effect of the complete absence of apoC1 on very-low-density lipoprotein (VLDL)-TG lipolysis, clearance and production, by performing studies with the previously generated apoC1-deficient mice. On a sucrose-rich, low fat/low cholesterol (LFC) diet, apoC1-deficient mice accumulate in their circulation VLDL particles, which contain relatively lower amounts of lipids when compared with VLDL isolated from control mice. Lipolysis assays in vitro on VLDL from apoC1-deficient and control mice showed no differences in apparent K(m) and Vmax values (0.27 +/- 0.06 versus 0.24 +/- 0.03 mmol of TG/litre and 0.40 +/- 0.03 versus 0.36 +/- 0.03 mmol of non-esterified fatty acid (NEFA)/min per litre respectively). To correct for potential differences in the size of the VLDL particles, the resulting K(m) values were also expressed relative to apoB concentration. Under these conditions apoC1-deficient VLDL displayed a lower, but not significant, K(m) value when compared with control VLDL (3.44 +/- 0.71 versus 4.44 +/- 0.52 mmol of TG2/g apoB per litre). VLDL turnover studies with autologous injections of [3H]TG-VLDL in vivo showed that the VLDL fractional catabolic rate (FCR) was decreased by up to 50% in the apoC1-deficient mice when compared with control mice (10.5 +/- 3.4 versus 21.0 +/- 1.2/h of pool TG). No significant differences between apoC1-deficient and control mice were observed in the hepatic VLDL production estimated by Triton WR139 injections (0.19 +/- 0.02 versus 0.21 +/- 0.05 mmol/h of TG per kg) and in the extra-hepatic lipolysis of VLDL-TG (4.99 +/- 1.62 versus 3.46 +/- 1.52/h of pool TG) in vivo. Furthermore, [125I]VLDL-apoB turnover experiments in vivo also showed a 50% decrease in the FCR of VLDL in apoC1-deficient mice when compared with control mice on the LFC diet (1.1 +/- 0.3 versus 2.1 +/- 0.1/h of pool apoB). When mice were fed a very high fat/high cholesterol (HFC) diet, the VLDL-apoB FCR was further decreased in apoC1-deficient mice (0.4 +/- 0.1 versus 1.4 +/- 0.4/h of pool apoB). We conclude that, in apoC1-deficient mice, the FCR of VLDL is reduced because of impaired uptake of VLDL remnants by hepatic receptors, whereas the production and lipolysis of VLDL-TG is not affected.
载脂蛋白（apo）C1在体内的功能尚未明确界定。由于过表达人apoC1的转基因小鼠表现出三酰甘油（TG）水平升高[Simonet、Bucay、Pitas、Lauer和Taylor（1991年）《生物化学杂志》266, 8651 - 8654]，因此有人提出apoC1在TG代谢中存在尚未明确的作用。在此，我们通过对先前培育出的apoC1缺陷小鼠进行研究，直接探究完全缺乏apoC1对极低密度脂蛋白（VLDL）-TG脂解、清除及生成的影响。在富含蔗糖的低脂/低胆固醇（LFC）饮食条件下，apoC1缺陷小鼠的循环中积累了VLDL颗粒，与从对照小鼠分离的VLDL相比，这些颗粒所含脂质相对较少。对apoC1缺陷小鼠和对照小鼠的VLDL进行体外脂解测定，结果显示表观K(m)值和Vmax值并无差异（分别为0.27±0.06与0.24±0.03 mmol TG/升，以及0.40±0.03与0.36±0.03 mmol非酯化脂肪酸（NEFA）/每分钟每升）。为校正VLDL颗粒大小的潜在差异，所得K(m)值也相对于apoB浓度进行表达。在这些条件下，与对照VLDL相比，apoC1缺陷的VLDL显示出较低但不显著的K(m)值（3.44±0.71与4.44±0.52 mmol TG2/g apoB每升）。体内自体注射[3H]TG - VLDL进行的VLDL周转研究表明，与对照小鼠相比，apoC1缺陷小鼠的VLDL分解代谢率（FCR）降低了多达50%（10.5±3.4与21.0±1.2/h的总池TG）。通过注射Triton WR139估计的肝脏VLDL生成量（每千克0.19±0.02与0.21±0.05 mmol TG/h）以及体内VLDL - TG的肝外脂解（4.99±1.62与3.46±1.52/h的总池TG），在apoC1缺陷小鼠和对照小鼠之间未观察到显著差异。此外，体内[125I]VLDL - apoB周转实验还表明，与LFC饮食的对照小鼠相比，apoC1缺陷小鼠中VLDL的FCR降低了50%（1.1±0.3与2.1±0.1/h的总池apoB）。当给小鼠喂食极高脂肪/高胆固醇（HFC）饮食时，apoC1缺陷小鼠的VLDL - apoB FCR进一步降低（0.4±0.1与1.4±0.4/h的总池apoB）。我们得出结论，在apoC1缺陷小鼠中，VLDL 的FCR降低是因为肝脏受体对VLDL残余物的摄取受损，而VLDL - TG的生成和脂解不受影响。
