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首页> 外文期刊>Journal of Lipid Research >Diurnal and dietary-induced changes in cholesterol synthesis correlate with levels of mRNA for HMG-CoA reductase.
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Diurnal and dietary-induced changes in cholesterol synthesis correlate with levels of mRNA for HMG-CoA reductase.

机译：胆固醇合成的日变化和饮食变化与HMG-CoA还原酶的mRNA水平相关。

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We determined the extent to which diurnal variation in cholesterol synthesis in liver is controlled by steady-state mRNA levels for the rate-limiting enzyme in the pathway, hydroxymethylglutaryl (HMG)-CoA reductase. Rats 30 days of age and maintained on a low-cholesterol diet since weaning were injected intraperitoneally with (3)H(2)O. The specific radioactivity of the whole-body water pool soon became constant, allowing for expression of values for incorporation of label into cholesterol as absolute rates of cholesterol synthesis. In liver, there was a peak of cholesterol synthesis from 8 pm to midnight, a 4-fold increase over synthesis rates from 8 am to noon. Increases in synthesis were quantitatively in lock step with increases in mRNA levels for HMG-CoA reductase occurring 4 h earlier. In a parallel experiment, rats received 1% cholesterol in the diet from weaning to 30 days of age. Basal levels of hepatic cholesterol synthesis were greatly diminished and there was little diurnal variation of cholesterol synthesis or of levels of mRNA for HMG-CoA reductase. Levels of mRNA for the low density lipoprotein receptor and scavenger receptor-B1 (putative high density lipoprotein receptor) showed little diurnal variation, regardless of diet. This suggests that diurnal variation of hepatic cholesterol synthesis is driven primarily by varying the steady-state mRNA levels for HMG-CoA reductase. Other tissues were also examined. Adrenal gland also showed a 4-fold diurnal increase in accumulation of recently synthesized cholesterol. In contrast to liver, however, there was little corresponding change in mRNA expression for HMG-CoA reductase. Much of this newly synthesized cholesterol may be of hepatic origin, imported into adrenal by SR-B1, whose mRNA was up-regulated 2-fold. In brain, there was no diurnal variation in either cholesterol synthesis or mRNA expression, and no influence of high- or low-cholesterol diets on synthesis rates or HMG-CoA reductase mRNA levels.
机译：我们确定了肝脏中胆固醇合成的昼夜变化受到该途径中限速酶羟甲基戊二酰（HMG）-CoA还原酶的稳态mRNA水平控制的程度。断奶后30天大的大鼠并保持低胆固醇饮食，并向其腹膜内注射（3）H（2）O。全身水池的比放射性很快变得恒定，可以表达将标记掺入胆固醇的值，即胆固醇合成的绝对速率。在肝脏中，从晚上8点到午夜，胆固醇合成达到峰值，比从早上8点到中午的合成速率高4倍。合成的增加在定量上与HMG-CoA还原酶的mRNA水平增加在4个小时之前处于锁定阶段。在平行实验中，从断奶到30天龄，大鼠饮食中胆固醇的含量为1％。肝脏胆固醇合成的基础水平大大降低，胆固醇合成或HMG-CoA还原酶的mRNA水平几乎没有昼夜变化。无论饮食如何，低密度脂蛋白受体和清道夫受体-B1（假定的高密度脂蛋白受体）的mRNA水平均未见昼夜变化。这表明肝脏胆固醇合成的日变化主要是通过改变HMG-CoA还原酶的稳态mRNA水平来驱动的。还检查了其他组织。肾上腺还显示最近合成的胆固醇的累积日增4倍。但是，与肝脏相反，HMG-CoA还原酶的mRNA表达几乎没有变化。这种新合成的胆固醇中的大部分可能是肝脏来源的，通过SR-B1输入到肾上腺，其mRNA上调了2倍。在大脑中，胆固醇合成或mRNA表达均无昼夜变化，高胆固醇或低胆固醇饮食对合成速率或HMG-CoA还原酶mRNA水平均无影响。

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