Mayorek N, Bar-Tana J
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Biochem J. 1993 Feb 1;289 ( Pt 3)(Pt 3):911-7. doi: 10.1042/bj2890911.
Treatment of cholesterol-fed male hamsters kept on a diet of purina chow with beta beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a progressive hypocholesterolaemic effect, amounting to a 50% decrease in the cholesterol content of all plasma lipoproteins. The decrease in plasma cholesterol could be accounted for by activation of plasma-cholesterol efflux through the liver into the bile mediated by MEDICA 16-induced (a) increase of the number of liver LDL receptors, (b) activation of liver neutral cholesteryl ester hydrolase with a concomitant inhibition of liver acyl-CoA cholesterol acyltransferase, resulting in shifting of the liver cholesteryl ester/free-cholesterol cycle in the direction of free cholesterol, and (c) activation of cholesterol efflux from the liver into the bile. The increase in bile cholesterol output was accompanied by an increase in bile phospholipids but not in bile acids. In contrast with rats, MEDICA 16-treatment of male hamsters did not result in a hypotriacylglycerolaemic effect, inhibition of lipogenesis, nor in a substantial decrease in plasma apolipoprotein C-III content.
用β,β'-甲基取代的十六烷二酸（MEDICA 16）对食用普瑞纳饲料的雄性仓鼠进行治疗，会产生渐进性的降胆固醇作用，所有血浆脂蛋白的胆固醇含量降低了50%。血浆胆固醇的降低可归因于MEDICA 16诱导的以下作用介导的血浆胆固醇通过肝脏向胆汁的流出激活：（a）肝脏低密度脂蛋白受体数量增加；（b）肝脏中性胆固醇酯水解酶激活，同时肝脏酰基辅酶A胆固醇酰基转移酶受到抑制，导致肝脏胆固醇酯/游离胆固醇循环向游离胆固醇方向转变；（c）胆固醇从肝脏向胆汁的流出激活。胆汁胆固醇输出的增加伴随着胆汁磷脂的增加，但胆汁酸没有增加。与大鼠不同，用MEDICA 16治疗雄性仓鼠不会产生降甘油三酯作用、抑制脂肪生成，也不会使血浆载脂蛋白C-III含量大幅降低。
