LPS decreases fatty acid oxidation and nuclear hormone receptors in the kidney.
LPS decreases fatty acid oxidation and nuclear hormone receptors in the kidney.
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DOI：
10.1194/jlr.m800233-jlr200
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发表时间：
2008-10
影响因子：
6.5
通讯作者：
Grunfeld, Carl
中科院分区：
文献类型：
--
作者：
Feingold, Kenneth R.;Wang, Yuwei;Moser, Arthur;Shigenaga, Judy K.;Grunfeld, Carl
关键词：
炎症引起脂质代谢的显著变化，包括血清脂肪酸（FA）和甘油三酯（TG）增加，肝脏TG产生和VLDL分泌增加，脂肪组织脂解增加，以及肝脏和心脏中FA氧化减少。脂多糖（LPS）也增加肾脏中的TG和胆固醇酯水平。在这里，我们证实了这些发现，并定义了潜在的机制。LPS使肾FA氧化降低40%，并降低FA氧化所需的关键蛋白质的表达，包括FA转运蛋白-2、脂肪酰辅酶A合酶、肉毒碱棕榈酰转移酶-1、中链酰基辅酶A脱氢酶和酰基辅酶A氧化酶。在过氧化物酶体增殖物激活受体α（PPARα）缺陷小鼠中观察到类似的降低。LPS还导致肾脏PPARα（降低75%）、甲状腺激素受体α（TRα）（降低92%）和TRβ（降低84%）mRNA水平降低，而PPARβ/δ和γ没有改变。在LPS处理小鼠的肾脏中，PGC 1 α和β（PPARs和TR所需的共激活因子）的表达也降低，PGC 1调节的线粒体基因（Atp 5g 1、COX 5a、Idh 3a和Ndufs 8）也是如此。肾脏FA氧化减少可能是全身协调宿主反应的副产物，以增加可用于宿主防御和/或组织修复的FA和TG。然而，肾脏需要能量来支持其运输功能，并且不能通过FA氧化产生能量可能导致严重脓毒症中观察到的肾衰竭。
Inflammation produces marked changes in lipid metabolism, including increased serum fatty acids (FAs) and triglycerides (TGs), increased hepatic TG production and VLDL secretion, increased adipose tissue lipolysis, and decreased FA oxidation in liver and heart. Lipopolysaccharide (LPS) also increases TG and cholesteryl ester levels in kidneys. Here we confirm these findings and define potential mechanisms. LPS decreases renal FA oxidation by 40% and the expression of key proteins required for oxidation of FAs, including FA transport protein-2, fatty acyl-CoA synthase, carnitine palmitoyltransferase-1, medium-chain acyl-CoA dehydrogenase, and acyl-CoA oxidase. Similar decreases were observed in peroxisome proliferator-activated receptor α (PPARα)-deficient mice. LPS also caused a reduction in renal mRNA levels of PPARα (75% decrease), thyroid hormone receptor α (TRα) (92% decrease), and TRβ (84% decrease), whereas PPARβ/δ and γ were not altered. Expression of PGC1 α and β, coactivators required for PPARs and TR, was also decreased in kidneys of LPS-treated mice, as were mitochondrial genes regulated by PGC1 (Atp5g1, COX5a, Idh3a, and Ndufs8). Decreased renal FA oxidation could be a by-product of the systemic coordinated host response to increase FAs and TGs available for host defense and/or tissue repair. However, the kidney requires energy to support its transport functions, and the inability to generate energy via FA oxidation might contribute to the renal failure seen in severe sepsis.