Discovery of the lipoproteins, their role in fat transport and their significance as risk factors
Discovery of the lipoproteins, their role in fat transport and their significance as risk factors
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DOI：
10.1093/jn/128.2.439s
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发表时间：
1998-02-01
影响因子：
4.2
通讯作者：
Olson, RE
中科院分区：
文献类型：
--
作者：
Olson, RE
哺乳动物血浆中的脂肪运输系统的想法在三个世纪中缓慢发展。在本世纪之交，人们发现血浆球蛋白中含有卵磷脂，并且用胃蛋白酶消化血浆蛋白会释放出少量的脂肪和胆固醇。高密度脂蛋白（HDL）于1929年首次从马血清中分离出来，低密度脂蛋白（LDL）于1950年首次从马血清中分离出来。然后显示，在超浓缩器中漂浮血浆揭示了一系列脂蛋白，包括VLDL、LDL和HDL，并允许定量。随后，发现血浆中游离脂肪酸（FFA）与白蛋白结合，并随进食和禁食而变化。从进一步的研究中可以得出结论，脂蛋白结合的甘油三酯在餐后被输送到脂肪细胞进行摄取;在禁食期间，脂肪细胞分泌FFA，为许多组织提供燃料。脂蛋白（载脂蛋白肽）的蛋白质组分在1960年至1970年期间进行了表征，LDL受体在1974年被鉴定。然后建立脂肪转运作为脂蛋白到靶组织的受体介导的递送系统，由于基因改变或缺乏受体导致的该系统中的缺陷解释了血脂异常，其促进动脉粥样硬化、黄瘤病和阿尔茨海默病。
The idea of a fat transport system in the plasma of mammals evolved slowly over three centuries. At the turn of this century, it was discovered that plasma globulins contained lecithin and that the digestion of plasma proteins with pepsin liberated small amounts of fat and cholesterol. The high density lipoprotein (HDL) was first isolated from horse serum in 1929 and the low density lipoprotein (LDL) in 1950. It was then shown that flotation of plasma in the ultracentrifuge revealed an array of lipoproteins that included VLDL, LDL and HDL and permitted quantitation. Subsequently, it was discovered that the free fatty acids (FFA) in plasma were bound to albumin and varied with feeding and fasting. From further studies, it was concluded that lipoprotein-bound triglycerides were delivered to adipose cells for uptake after meals; during fasting, the fat cells secreted FFA, which provided fuel for many tissues. The protein components of the lipoproteins (apopeptides) were characterized in the period from 1960 to 1970 and the LDL-receptor was identified in 1974. Fat transport was then established as a receptor-mediated delivery system of lipoproteins to targeted tissues, Defects in this system due to genetically altered or absent receptors explained dyslipidemias, which promoted atherosclerosis, xanthomatosis and Alzheimer's disease.