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首页> 外文期刊>American Journal of Physiology >pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism
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pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism

机译：子宫内LXR的药理活化直接影响小鼠ABC转运蛋白的表达和功能，但不影响成年胆固醇的代谢

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Pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism. .-Cholesterol is critical for several cellular functions and essential for normal fetal development. Therefore, its metabolism is tightly con-trolled during all life stages. The liver X receptors-alpha (LXRalpha; NR1H3) and -beta (LXRbeta; NR1H2) are nuclear receptors that are of key rele-vance in coordinating cholesterol and fatty acid metabolism. The aim of this study was to elucidate whether fetal cholesterol metabolism can be influenced in utero via pharmacological activation of LXR and whether this would have long-term effects on cholesterol homeostasis. Administration of the LXR agonist T0901317 to pregnant mice via their diet (0.015% wt/wt) led to induced fetal hepatic expression levels of the cholesterol transporter genes Abcg5/g8 and Abcal, higher plasma cholesterol levels, and lower hepatic cholesterol levels com-pared with controls. These profound changes during fetal develop-ment did not affect cholesterol metabolism in adulthood nor did they influence coping with a high-fat/high-cholesterol diet. This study shows that the LXR system is functional in fetal mice and susceptible to pharmacological activation. Despite massive changes in fetal cho-lesterol metabolism, regulatory mechanisms involved in cholesterol metabolism return to a "normal" state in offspring and allow coping with a high-fat/high-cholesterol diet.
机译：子宫内LXR的药理活化直接影响小鼠中ABC转运蛋白的表达和功能，但不影响成年胆固醇的代谢。 .-胆固醇对于多种细胞功能至关重要，对正常胎儿发育至关重要。因此，其代谢在所有生命阶段都受到严格控制。肝脏X受体-α（LXRalpha; NR1H3）和-β（LXRbeta; NR1H2）是核受体，它们在协调胆固醇和脂肪酸代谢方面具有重要作用。这项研究的目的是阐明是否可以通过药理激活LXR来影响子宫内胎儿胆固醇的代谢，以及这是否会对胆固醇体内平衡产生长期影响。通过饮食（0.015％wt / wt）向怀孕小鼠施用LXR激动剂T0901317导致胎盘中胆固醇转运蛋白Abcg5 / g8和Abcal的肝表达水平升高，血浆胆固醇水平升高，肝胆固醇水平降低与控件。胎儿发育过程中的这些深刻变化既不影响成年期的胆固醇代谢，也不影响高脂/高胆固醇饮食的应对。这项研究表明，LXR系统在胎儿小鼠中具有功能，并且易于药理激活。尽管胎儿胆固醇的代谢发生了巨大变化，但参与胆固醇代谢的调节机制在后代中恢复了“正常”状态，并允许应对高脂/高胆固醇饮食。

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