Hennessy L K, Osada J, Ordovas J M, Nicolosi R J, Stucchi A F, Brousseau M E, Schaefer E J
USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
J Lipid Res. 1992 Mar;33(3):351-60.
The effects of the long-term administration of the dietary fats coconut oil and corn oil at 31% of calories with or without 0.1% (wt/wt) dietary cholesterol on plasma lipoproteins, apolipoproteins (apo), hepatic lipid content, and hepatic apoA-I, apoB, apoE, and low density lipoprotein (LDL) receptor mRNA abundance were examined in 27 cebus monkeys. Relative to the corn oil-fed animals, no significant differences were noted in any of the parameters of the corn oil plus cholesterol-fed group. In animals fed coconut oil without cholesterol, significantly higher (P less than 0.05) plasma total cholesterol (145%), very low density lipoprotein (VLDL) + LDL (201%) and high density lipoprotein (HDL) (123%) cholesterol, apoA-I (103%), apoB (61%), and liver cholesteryl ester (263%) and triglyceride (325%) levels were noted, with no significant differences in mRNA levels relative to the corn oil only group. In animals fed coconut oil plus cholesterol, all plasma parameters were significantly higher (P less than 0.05), as were hepatic triglyceride (563%) and liver apoA-I (123%) and apoB (87%) mRNA levels relative to the corn oil only group, while hepatic LDL receptor mRNA (-29%) levels were significantly lower (P less than 0.05). Correlation coefficient analyses performed on pooled data demonstrated that liver triglyceride content was positively associated (P less than 0.05) with liver apoA-I and apoB mRNA levels and negatively associated (P less than 0.01) with hepatic LDL receptor mRNA levels. Liver free and esterified cholesterol levels were positively correlated (P less than 0.05) with liver apoE mRNA levels and negatively correlated (P less than 0.025) with liver LDL receptor mRNA levels. Interestingly, while a significant correlation (P less than 0.01) was noted between hepatic apoA-I mRNA abundance and plasma apoA-I levels, no such relationship was observed between liver apoB mRNA and plasma apoB levels, suggesting that the hepatic mRNA of apoA-I, but not that of apoB, is a major determinant of the circulating levels of the respective apolipoprotein. Our data indicate that a diet high in saturated fat and cholesterol may increase the accumulation of triglyceride and cholesterol in the liver, each resulting in the suppression of hepatic LDL receptor mRNA levels. We hypothesize that such elevations in hepatic lipid content differentially alter hepatic apoprotein mRNA levels, with triglyceride increasing hepatic mRNA concentrations for apoA-I and B and cholesterol elevating hepatic apoE mRNA abundance.
在27只卷尾猴中研究了长期给予占热量31%的膳食脂肪（椰子油和玉米油），添加或不添加0.1%（重量/重量）膳食胆固醇对血浆脂蛋白、载脂蛋白（apo）、肝脏脂质含量以及肝脏apoA-I、apoB、apoE和低密度脂蛋白（LDL）受体mRNA丰度的影响。相对于喂食玉米油的动物，喂食玉米油加胆固醇组的任何参数均未观察到显著差异。在喂食不含胆固醇的椰子油的动物中，血浆总胆固醇（145%）、极低密度脂蛋白（VLDL）+低密度脂蛋白（201%）和高密度脂蛋白（HDL）（123%）胆固醇、apoA-I（103%）、apoB（61%）以及肝脏胆固醇酯（263%）和甘油三酯（325%）水平显著更高（P<0.05），相对于仅喂食玉米油的组，mRNA水平无显著差异。在喂食椰子油加胆固醇的动物中，所有血浆参数均显著更高（P<0.05），相对于仅喂食玉米油的组，肝脏甘油三酯（563%）以及肝脏apoA-I（123%）和apoB（87%）mRNA水平也显著更高，而肝脏LDL受体mRNA（-29%）水平显著更低（P<0.05）。对汇总数据进行的相关系数分析表明，肝脏甘油三酯含量与肝脏apoA-I和apoB mRNA水平呈正相关（P<0.05），与肝脏LDL受体mRNA水平呈负相关（P<0.01）。肝脏游离胆固醇和酯化胆固醇水平与肝脏apoE mRNA水平呈正相关（P<0.05），与肝脏LDL受体mRNA水平呈负相关（P<0.025）。有趣的是，虽然观察到肝脏apoA-I mRNA丰度与血浆apoA-I水平之间存在显著相关性（P<0.01），但未观察到肝脏apoB mRNA与血浆apoB水平之间存在此类关系，这表明apoA-I的肝脏mRNA而非apoB的肝脏mRNA是各自载脂蛋白循环水平的主要决定因素。我们的数据表明，高饱和脂肪和胆固醇饮食可能会增加肝脏中甘油三酯和胆固醇的积累，每种情况都会导致肝脏LDL受体mRNA水平受到抑制。我们推测，肝脏脂质含量的这种升高会差异性地改变肝脏载脂蛋白mRNA水平，甘油三酯会增加apoA-I和B的肝脏mRNA浓度，胆固醇会提高肝脏apoE mRNA丰度。
