Hepatic fatty acid and cholesterol metabolism in nephrotic syndrome.
Hepatic fatty acid and cholesterol metabolism in nephrotic syndrome.
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DOI：
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发表时间：
2013-03
影响因子：
2.2
通讯作者：
Seungyeup Han;N. Vaziri;P. Gollapudi;V. Kwok;H. Moradi
中科院分区：
文献类型：
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作者：
Seungyeup Han;N. Vaziri;P. Gollapudi;V. Kwok;H. Moradi
大量蛋白尿（肾病综合征）与高胆固醇血症、高胆固醇血症和动脉粥样硬化的高风险有关。肾病综合征（NS）的高甘油三酯血症部分是由于TG和富含TG的脂蛋白产生增加。然而，关于NS对脂肪酸产生和分解代谢机制的影响的数据是有限的。雄性Sprague道利大鼠腹腔注射嘌呤霉素氨基糖苷诱导NS。第二次注射后6周，对动物实施安乐死，收获肝脏并进行处理。NS组出现大量蛋白尿、高胆固醇血症、高甘油三酯血症，SREBP-1和LXR α/β激活，FAS、ACC和HMG CoA还原酶表达上调。与此相反，肝组织ChREBP活性降低NS排除其在FA合成途径上调的作用。尽管在肾病动物的肝脏中增加了PPARα的表达和核转位，但是ACO的表达以及CPT和L-FABP的丰度降低。因此，NS导致FA生产机制的上调。NS中肝脏脂肪酸生成能力增加与FA催化剂减少有关，这些事件导致相关的高甘油三酯血症。
Heavy proteinuria (nephrotic syndrome) is associated with hypercholesterolemia, hypertriglyceridemia and a high risk of atherosclerosis. Hypertriglyceridemia in nephrotic syndrome (NS) is partly due to increased TG and TG-rich lipoprotein production. However, data on the effect of NS on fatty acid production and catabolic machinery are limited. NS was induced in male Sprague Dawley rats by IP injection of puromycin aminonucleoside. Six weeks after the second injection the animals were euthanized, liver was harvested and processed. The NS group exhibited heavy proteinuria, hypercholesterolemia, hypertriglyceridemia, activation of SREBP-1 and LXR α/β, up-regulation of FAS, ACC and HMG CoA reductase. In contrast hepatic tissue ChREBP activity was reduced in NS excluding its role in upregulation of FA synthetic pathway. Despite increased expression and nuclear translocation of PPARα, expression of ACO and abundance of CPT and L-FABP, were decreased in the liver of nephrotic animals. Therefore, NS results in upregulation of FA production machinery. Increased hepatic fatty acid production capacity in NS is compounded by reduced FA catabolism, events that contribute to the associated hypertiglyceridemia.