瘦型和肥胖型 Zucker 雌性大鼠体内及单通道灌注肝脏标本中的脂蛋白分泌

Petit D, Wang S R, Renaud G, Infante R

INSERM Unit 9 Hepatology, Paris, France.

Arch Int Physiol Biochim. 1988 Mar;96(1):51-62. doi: 10.3109/13813458809079625.

The plasma lipoprotein composition as well as lipoprotein synthesis and secretion were studied in vivo and in a single-pass-perfused liver preparation in lean and obese Zucker rats. Compared with their lean littermates the levels in the plasma of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) + low density lipoprotein (LDL) and high density lipoprotein (HDL) were increased 4-, 2- and 2.5 fold, respectively, in obese rats. In these rats both VLDL and IDL + LDL were enriched in triglycerides, while the HDL were enriched in cholesterol. Although the VLDL and IDL + LDL protein concentrations were the same in lean and obese rats, the HDL protein concentration was 3-fold greater in the obese rats. Both the lean and obese rats incorporated similar amounts of [14C]leucine into total liver protein. However, obese rats incorporated 2.5-fold and 6-fold more [14C]leucine into VLDL and HDL in vivo, 2.7-fold and 1.7 fold more [35S]methionine in VLDL and HDL present in the perfusate, than did lean rats. The perfusate [35S]S-labelled apoproteins (apo-B100, B48; apo-E, apo-AI, apo-AIV and apo-C) were separated by gel electrophoresis and identified by autoradiography. Incorporation of [3H]glycerol into liver, VLDL, IDL + LDL and HDL triglycerides was 2-, 48-, 13- and 1.5-fold higher in obese than in lean rats, respectively. The [3H]-labelled triglycerides in VLDL and IDL + LDL present in the perfusate was 5.4-fold and 4.4-fold more in obese rat. There was no difference in the incorporation of [3H]glycerol into triglycerides of perfusate HDL between the two genotypes of rats. Thus, the hypertriglyceridaemia observed in obese Zucker rats results from very high synthetic rates of both the lipid and protein moieties of plasma lipoproteins. Before this study, no report of the simultaneous triglycerides and protein synthesis in vivo and in a single-pass-perfused liver preparations had been reported.

在瘦型和肥胖型 Zucker 大鼠体内以及单通道灌注肝脏标本中，研究了血浆脂蛋白组成以及脂蛋白的合成与分泌。与瘦型同窝大鼠相比，肥胖大鼠血浆中极低密度脂蛋白（VLDL）、中间密度脂蛋白（IDL）+低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的水平分别升高了 4 倍、2 倍和 2.5 倍。在这些大鼠中，VLDL 和 IDL + LDL 的甘油三酯含量增加，而 HDL 的胆固醇含量增加。尽管瘦型和肥胖型大鼠的 VLDL 以及 IDL + LDL 蛋白浓度相同，但肥胖大鼠的 HDL 蛋白浓度却是瘦型大鼠的 3 倍。瘦型和肥胖型大鼠将相似量的[14C]亮氨酸掺入总肝蛋白中。然而，肥胖大鼠在体内将[14C]亮氨酸掺入 VLDL 和 HDL 的量分别比瘦型大鼠多 2.5 倍和 6 倍，在灌注液中的 VLDL 和 HDL 中掺入的[35S]甲硫氨酸分别比瘦型大鼠多 2.7 倍和 1.7 倍。通过凝胶电泳分离灌注液中[35S]标记的载脂蛋白（apo-B100、B48；apo-E、apo-AI、apo-AIV 和 apo-C），并通过放射自显影进行鉴定。肥胖大鼠肝脏、VLDL、IDL + LDL 和 HDL 甘油三酯中[3H]甘油的掺入量分别比瘦型大鼠高 2 倍、48 倍、13 倍和 1.5 倍。灌注液中 VLDL 和 IDL + LDL 中[3H]标记的甘油三酯在肥胖大鼠中分别多 5.4 倍和 4.4 倍。两种基因型大鼠灌注液 HDL 的甘油三酯中[3H]甘油的掺入量没有差异。因此，肥胖 Zucker 大鼠中观察到的高甘油三酯血症是由于血浆脂蛋白的脂质和蛋白质部分的合成速率都非常高所致。在本研究之前，尚未有关于体内以及单通道灌注肝脏标本中同时进行甘油三酯和蛋白质合成的报道。