Pocathikorn Anothai, Taylor Roger R, James Ian, Mamotte Cyril D S
Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia 6000.
J Nutr. 2007 Sep;137(9):2062-7. doi: 10.1093/jn/137.9.2062.
Little is known about the immediate effects of dietary fat on the expression of genes involved in cholesterol metabolism in humans. We investigated the effects of a high-fat meal on circulating mononuclear cell messenger RNA (mRNA) for the LDL receptor (LDLR), LDLR-related protein (LRP), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) over 10 h. Selection of 12 C and 7 T homozygotes for the LRP exon 22 C200T polymorphism for the study also enabled us to examine the influence of this polymorphism on postprandial mRNA expression and lipoproteins, of relevance because of LRP's role in postprandial lipoprotein metabolism and association of the polymorphism with coronary artery disease. We found a postprandial decrease in LDLR mRNA abundance relative to the reference beta-actin (BA) mRNA. The decreased LDLR/BA mRNA value was apparent at 1 h (P < 0.005) and decreased to 25% of baseline at 6 h (P < 0.005). The LRP/BA mRNA value was also lower at 6 h (16% decrease, P < 0.05). HMGCR mRNA expression was unchanged. C homozygotes for the C200T polymorphism had higher LDLR/BA values than T homozygotes (P = 0.01) and although plasma LDL cholesterol (LDL-C) concentrations decreased in the postprandial period (P < 0.002), the decrease was less in C than in T homozygotes (P < 0.05). This study constitutes the first observation, to our knowledge, of postprandial changes in LDLR and LRP mRNA expression. It documents immediate effects of a fatty meal on these mRNA as well as an LRP genotype effect on LDLR mRNA and LDL-C.
关于饮食脂肪对人类胆固醇代谢相关基因表达的即时影响，目前所知甚少。我们研究了高脂餐对循环单核细胞中低密度脂蛋白受体（LDLR）、LDLR相关蛋白（LRP）和3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）信使核糖核酸（mRNA）在10小时内的影响。选择12名携带LRP外显子22 C200T多态性的C纯合子和7名T纯合子进行研究，这也使我们能够研究这种多态性对餐后mRNA表达和脂蛋白的影响，鉴于LRP在餐后脂蛋白代谢中的作用以及该多态性与冠状动脉疾病的关联，这具有重要意义。我们发现，相对于参考β-肌动蛋白（BA）mRNA，餐后LDLR mRNA丰度下降。LDLR/BA mRNA值在1小时时明显下降（P < 0.005），在6小时时降至基线的25%（P < 0.005）。LRP/BA mRNA值在6小时时也较低（下降16%，P < 0.05）。HMGCR mRNA表达未发生变化。C200T多态性的C纯合子的LDLR/BA值高于T纯合子（P = 0.01），并且尽管餐后血浆低密度脂蛋白胆固醇（LDL-C）浓度下降（P < 0.002），但C纯合子的下降幅度小于T纯合子（P < 0.05）。据我们所知，本研究首次观察到餐后LDLR和LRP mRNA表达的变化。它记录了脂肪餐对这些mRNA的即时影响以及LRP基因型对LDLR mRNA和LDL-C的影响。
