Sorci-Thomas M, Wilson M D, Johnson F L, Williams D L, Rudel L L
Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
J Biol Chem. 1989 May 25;264(15):9039-45.
African green monkeys were fed diets containing low and moderate cholesterol concentrations with either polyunsaturated or unsaturated fat as 40% of calories. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol, and apoB concentrations generally were higher in animals fed (a) the higher dietary cholesterol concentration and (b) saturated fat. At necropsy, liver and intestine were removed, and measurement of mRNAs for LDL receptors (liver) and for apolipoprotein B (liver and intestine) was done. Monkey small intestine mucosa made exclusively apoB48 while the liver made only apoB100, although apoB mRNA in both tissues was the same size (14 kilobases). No dietary cholesterol or fat effects were found for apoB mRNA abundance in the liver, while the animals fed the higher dietary cholesterol level had 50% lower levels of hepatic LDL receptor mRNA. In a separate group of animals, livers were perfused and the rate of apoB secretion was measured. No dietary fat effect on apoB secretion rate was found, and no relationship between plasma LDL cholesterol concentration and the rate of hepatic apoB production existed. These findings support the idea that the dietary factors that increase LDL concentrations act by reducing clearance of apoB-containing particles rather than by increasing production of these lipoproteins. Hepatic LDL receptor mRNA was similar in abundance in polyunsaturated fat and saturated fat-fed animals, suggesting that the difference in plasma cholesterol concentration between these groups is not mediated via effects on LDL receptor mRNA abundance. The level of intestinal apoB mRNA was about 30% higher in animals fed the moderate dietary cholesterol concentration. Earlier studies have shown that more cholesterol is transported in chylomicrons from the intestine when dietary cholesterol levels are higher, and the increased intestinal apoB mRNA abundance may reflect increased intestinal cholesterol transport and chylomicron apoB48 production.
给非洲绿猴喂食含有低胆固醇和中等胆固醇浓度的饮食，其中多不饱和脂肪或不饱和脂肪占热量的40%。一般来说，喂食（a）较高饮食胆固醇浓度和（b）饱和脂肪的动物，其血浆总胆固醇、低密度脂蛋白（LDL）胆固醇和载脂蛋白B浓度更高。尸检时，取出肝脏和肠道，测量肝脏中LDL受体的mRNA以及肝脏和肠道中载脂蛋白B的mRNA。猴小肠黏膜仅产生载脂蛋白B48，而肝脏仅产生载脂蛋白B100，尽管两个组织中的载脂蛋白B mRNA大小相同（14千碱基）。未发现饮食胆固醇或脂肪对肝脏中载脂蛋白B mRNA丰度有影响，而喂食较高饮食胆固醇水平的动物肝脏LDL受体mRNA水平低50%。在另一组动物中，对肝脏进行灌注并测量载脂蛋白B的分泌速率。未发现饮食脂肪对载脂蛋白B分泌速率有影响，且血浆LDL胆固醇浓度与肝脏载脂蛋白B产生速率之间不存在相关性。这些发现支持这样一种观点，即增加LDL浓度的饮食因素是通过减少含载脂蛋白B颗粒的清除率来起作用的，而不是通过增加这些脂蛋白的产生。多不饱和脂肪喂养的动物和饱和脂肪喂养的动物肝脏中LDL受体mRNA的丰度相似，这表明这些组之间血浆胆固醇浓度的差异不是通过对LDL受体mRNA丰度的影响来介导的。喂食中等饮食胆固醇浓度的动物肠道载脂蛋白B mRNA水平约高30%。早期研究表明，当饮食胆固醇水平较高时，更多的胆固醇以乳糜微粒的形式从肠道运输出去，肠道载脂蛋白B mRNA丰度的增加可能反映了肠道胆固醇运输和乳糜微粒载脂蛋白B48产生的增加。
