Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages
Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages
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DOI：
10.1074/jbc.m113.524587
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发表时间：
2014-01-31
影响因子：
4.8
通讯作者：
Munford, Robert S.
中科院分区：
文献类型：
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作者：
Huang, Ying-ling;Morales-Rosado, Joel;Munford, Robert S.
背景：微生物激动剂如何诱导巨噬细胞长时间储存甘油三酯（TAG）尚不清楚。结果如下：Toll样受体（TLR）1/2、TLR 3和TLR 4激动剂增加脂肪酸摄取，增加TAG合成，减少脂解，增加TAG储存72 h。结论：TAG保留是对传感微生物的一种积极、多方面和持久的反应。重要性：长时间的TAG储存有助于泡沫细胞的形成。感染组织中的巨噬细胞可以感知微生物分子，从而显著改变其代谢。在一个看似矛盾的地方，这些关键的宿主防御细胞通常通过增加葡萄糖催化剂来做出反应，同时将脂肪酸（FA）作为甘油三酯（TAG）储存在脂滴中。我们使用负载追踪策略来研究促进TAG在鼠和人巨噬细胞中长期保留的机制。Toll样受体（TLR）1/2、TLR 3和TLR 4激动剂均诱导细胞保留TAG 3天。TAG保留时间延长伴随以下情况：（a）FA摄取增加和FA掺入TAG，酰基辅酶A合成酶长1（ACSL 1）和二酰基甘油酰基转移酶-2（DGAT 2）持续增加，（B）脂解和FA氧化减少，导致脂肪甘油三酯脂肪酶（ATGL）长期下降。TLR激动剂诱导的TAG储存是一个多方面的过程，在大多数早期促炎反应消退后持续很长时间，并可能有助于感染组织中脂质负载巨噬细胞的形成。
Background: How microbial agonists induce macrophages to store triglycerides (TAG) for prolonged periods was not known. Results: Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists increased fatty acid uptake, increased TAG synthesis, and decreased lipolysis, augmenting TAG storage for 72 h. Conclusion: TAG retention is an active, multifaceted, and long lasting response to sensing microbes. Significance: Prolonged TAG storage contributes to foam cell formation.Macrophages in infected tissues may sense microbial molecules that significantly alter their metabolism. In a seeming paradox, these critical host defense cells often respond by increasing glucose catabolism while simultaneously storing fatty acids (FA) as triglycerides (TAG) in lipid droplets. We used a load-chase strategy to study the mechanisms that promote long term retention of TAG in murine and human macrophages. Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists all induced the cells to retain TAG for 3 days. Prolonged TAG retention was accompanied by the following: (a) enhanced FA uptake and FA incorporation into TAG, with long lasting increases in acyl-CoA synthetase long 1 (ACSL1) and diacylglycerol acyltransferase-2 (DGAT2), and (b) decreases in lipolysis and FA -oxidation that paralleled a prolonged drop in adipose triglyceride lipase (ATGL). TLR agonist-induced TAG storage is a multifaceted process that persists long after most early pro-inflammatory responses have subsided and may contribute to the formation of lipid-laden macrophages in infected tissues.