Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice
Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice
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DOI：
10.1172/jci8283
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发表时间：
2000-06-01
影响因子：
15.9
通讯作者：
Shachter, NS
中科院分区：
文献类型：
--
作者：
Ebara, T;Conde, K;Shachter, NS
我们使用野生型（WT）小鼠和仅表达apoB-100（B100小鼠）或仅表达apoB-48（B48小鼠）的小鼠来检查链脲佐菌素诱导的糖尿病（DM）对含apoB-100和apoB-48的脂蛋白的影响。WT小鼠的血浆脂质随着DM的增加而增加，并且脂肪耐受性显著受损。脂蛋白谱显示糖尿病B48小鼠中VLDL水平升高和胆固醇富集，但B100小鼠中未显示。C载脂蛋白，特别是VLDL中的apoC-I增加。为了研究链脲佐菌素处理动物中apoB-48脂蛋白增加的基础，我们描述了脂蛋白代谢的几个参数。甘油三酯和载脂蛋白B生成率正常，血浆脂肪酶活性、极低密度脂蛋白糖胺聚糖结合和极低密度脂蛋白脂解也正常。然而，由于脂质体的捕获减少，β-VLDL清除率降低。而LRP活性是正常的，从治疗小鼠的肝脏纳入硫酸乙酰肝素蛋白聚糖（HSPG）比对照组显着减少硫酸盐。在高糖条件下培养的肝癌细胞（HepG 2）和内皮细胞也显示硫酸盐和氨基葡萄糖掺入HSPG的减少。来自糖尿病小鼠的肝脏的蛋白质印迹显示HSPG核心蛋白，串珠素的减少。DM患者餐后含apoB-48脂蛋白的清除延迟似乎是由于肝串珠素HSPG降低所致。
We used wild-type (WT) mice and mice engineered to express either apoB-100 only (B100 mice) or apoB-48 only (B48 mice) to examine the effects of streptozotocin-induced diabetes (DM) on apoB-100- and apoB-48-containing lipoproteins. Plasma lipids increased with DM in WT mice, and fat tolerance was markedly impaired. Lipoprotein profiles showed increased levels and cholesterol enrichment of VLDL in diabetic B48 mice but not in B100 mice. C apolipoproteins, in particular apoC-I in VLDL, were increased. To investigate the basis of the increase in apoB-48 lipoproteins in streptozotocin-treated animals, we characterized several parameters of lipoprotein metabolism. Triglyceride and apoB production rates were normal, as were plasma lipase activity, VLDL glycosaminoglycan binding, and VLDL lipolysis. However, beta-VLDL clearance decreased due to decreased trapping by the lit er. Whereas LRP activity was normal, livers from treated mice incorporated significantly less sulfate into heparan sulfate proteoglycans (HSPG) than did controls. Hepatoma (HepG2) cells and endothelial cells cultured in high glucose also showed decreased sulfate and glucosamine incorporation into HSPG. Western blots of livers from diabetic mice showed a decrease in the HSPG core protein, perlecan. Delayed clearance of postprandial apoB-48-containing lipoproteins in DM appears to be due to decreased hepatic perlecan HSPG.