Krul E S, Dolphin P J
Biochim Biophys Acta. 1982 Dec 13;713(3):609-21. doi: 10.1016/0005-2760(82)90321-6.
The induction of hypothyroidism in the rat is necessary for the development of pronounced dietary-induced hypercholesterolemia. The nature of nascent lipoproteins secreted by isolated hepatocytes from euthyroid, hypothyroid and hypothyroid, cholesterol-fed rats was investigated to distinguish between these hormonal and dietary effects. Serum total lipids, apolipoproteins, B, E and A-I, were greatly elevated in hypercholesterolemia. In hypothyroidism, serum apolipoproteins B and E were elevated, triacylglycerols were reduced by 65% and free cholesterol was increased by 50%. The total lipid, apolipoprotein B and E, secreted by hypercholesterolemic rat hepatocytes was markedly elevated when compared to normal. Triacylglycerol and phospholipid secretion was slightly increased by hypothyroid rat hepatocytes; however, apolipoprotein B, E and A-I secretion rates were unaffected. Gel filtration of the nascent lipoproteins demonstrated that compared to normal, proportionately more apolipoprotein B and E from hypercholesterolemic rat hepatocytes and apolipoprotein E from hypothyroid rat hepatocytes was secreted as larger lipoproteins. Hypercholesterolemic rat hepatocytes secreted abnormal cholesterol-rich particles even after 24 h of incubation in a lipid-deficient medium. Hypothyroidism alone cannot account for this observation, as hypothyroid rat hepatocytes secreted a triacylglycerol-rich, cholesterol-deficient lipoprotein having a normal nascent lipoprotein lipid composition. These observations are consistent with the hypothesis that in hypothyroidism the accumulation of beta-migrating lipoproteins results from impaired removal of lipoprotein catabolites from the serum, a condition which would only promote hypercholesterolemia in cholesterol feeding where direct synthesis of abnormal lipoproteins occurs.
在大鼠中诱发甲状腺功能减退对于显著的饮食诱导性高胆固醇血症的发展是必要的。研究了来自正常甲状腺、甲状腺功能减退和甲状腺功能减退且喂食胆固醇的大鼠的分离肝细胞分泌的新生脂蛋白的性质，以区分这些激素和饮食的影响。高胆固醇血症时血清总脂质、载脂蛋白B、E和A-I显著升高。在甲状腺功能减退时，血清载脂蛋白B和E升高，三酰甘油降低65%，游离胆固醇增加50%。与正常情况相比，高胆固醇血症大鼠肝细胞分泌的总脂质、载脂蛋白B和E明显升高。甲状腺功能减退大鼠肝细胞的三酰甘油和磷脂分泌略有增加；然而，载脂蛋白B、E和A-I的分泌率未受影响。对新生脂蛋白进行凝胶过滤表明，与正常情况相比，高胆固醇血症大鼠肝细胞分泌的载脂蛋白B和E以及甲状腺功能减退大鼠肝细胞分泌的载脂蛋白E中，以较大脂蛋白形式分泌的比例更高。即使在脂质缺乏的培养基中孵育24小时后，高胆固醇血症大鼠肝细胞仍分泌异常的富含胆固醇的颗粒。仅甲状腺功能减退不能解释这一观察结果，因为甲状腺功能减退大鼠肝细胞分泌的是富含三酰甘油、缺乏胆固醇的脂蛋白，其新生脂蛋白脂质组成正常。这些观察结果与以下假设一致：在甲状腺功能减退时，β迁移脂蛋白的积累是由于血清中脂蛋白分解代谢产物清除受损所致，这种情况只会在发生异常脂蛋白直接合成的胆固醇喂养中促进高胆固醇血症。
