Obesity activates toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue of mice
Obesity activates toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue of mice
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DOI：
10.1016/j.jnutbio.2010.10.012
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发表时间：
2012-02-01
影响因子：
5.6
通讯作者：
Park, Taesun
中科院分区：
文献类型：
--
作者：
Kim, Seung-Jin;Choi, Youngshim;Park, Taesun
肥胖的特征是低级别和慢性炎症，这一现象可以用一个新的术语--代谢反应来解释。最近的研究表明，脂肪细胞可能通过Toll样受体(Toll-like Receptor，TLR)信号通路在脂肪沉积的免疫反应的生理调节中发挥重要作用。本研究通过研究TLR及其下游信号分子的组织特异性表达谱，探讨内脏和皮下脂肪组织在代谢过程中的作用，并探讨TLR介导的促炎信号级联反应对饮食诱导的肥胖(DIO)和由瘦素基因缺陷诱导的肥胖的不同反应。高脂饮食或瘦素缺乏诱导的肥胖上调小鼠脂肪组织中TLR1-9和TLR11-13的表达，这一现象与下游核因子kappa B、干扰素调节因子和STAT-1激活有关，并通过MyD88依赖和MyD88非依赖的级联反应上调细胞因子和趋化因子的表达。肥胖诱导的大多数TLR基因的上调和相关的促炎信号级联在附睾部脂肪组织中的程度远远大于在皮下脂肪组织中。此外，肥胖诱导的内脏脂肪组织中TLR1、TLR4、TLR5、TLR8、TLR9和TLR12基因以及大部分下游信号分子和靶细胞因子基因的上调幅度在DIO小鼠中大于BLOB小鼠。这些结果表明，TLRs和相关的促炎信号分子在肥胖症相关的代谢现象中可能起着重要作用。(C)2012 Elsevier Inc.保留所有权利。
Obesity is characterized by low-grade and chronic inflammation, a phenomenon explained with a new term, metaflammation. Recent studies suggest that adipocytes may play an important role in the physiological regulation of immune responses in fat deposits via toll-like receptor (TLR) signaling cascades. This study investigates the role of the visceral as well as subcutaneous adipose tissues in the development of metaflammation by characterizing the tissue-specific expression profiles of TLRs and downstream signaling molecules and explores the differential responsiveness of TLR-mediated proinflammatory signaling cascades to diet-induced obesity (DIO) and obesity induced by a leptin gene deficiency. The obesity that was induced by a high-fat diet or leptin deficiency up-regulated the expression of TLR1-9 and TLR11-13 in murine adipose tissues, a phenomenon linked with downstream nuclear factor kappa B, interferon regulatory factors, and STAT-1 activation, and up-regulated the expression of cytokines and chemokines via MyD88-dependent and MyD88-independent cascades. The extent of the obesity-induced up-regulation of most TLR genes and related proinflammatory signaling cascades was much greater in the epididymal adipose tissues than in the subcutaneous fat tissues of the mice with DIO. Furthermore, the magnitudes of the obesity-induced up-regulation of the TLR1, TLR4, TLR5, TLR8, TLR9, and TLR12 genes and most of the downstream signaling molecules and target cytokine genes in the visceral adipose tissue were greater in the DIO mice than in the blob mice. These results suggest that TLRs and related proinflammatory signaling molecules that are overexpressed in enlarged adipose tissues may play an important role in the obesity-associated phenomenon of metaflammation. (C) 2012 Elsevier Inc. All rights reserved.