Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University, Seoul 120-749, Korea.
J Nutr Biochem. 2012 Feb;23(2):113-22. doi: 10.1016/j.jnutbio.2010.10.012. Epub 2011 Mar 16.
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 κB, 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 ob/ob 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.
肥胖的特征是低度和慢性炎症，这种现象可以用一个新术语来解释，即代谢性炎症。最近的研究表明，脂肪细胞可能通过 toll 样受体 (TLR) 信号级联在脂肪组织中免疫反应的生理调节中发挥重要作用。本研究通过描述 TLR 和下游信号分子的组织特异性表达谱，研究内脏和皮下脂肪组织在代谢性炎症发展中的作用，并探讨 TLR 介导的促炎信号级联对饮食诱导肥胖 (DIO) 和瘦素基因缺乏引起肥胖的不同反应。高脂肪饮食或瘦素缺乏诱导的肥胖上调了小鼠脂肪组织中 TLR1-9 和 TLR11-13 的表达，这种现象与下游核因子 κB、干扰素调节因子和 STAT-1 激活有关，并通过 MyD88 依赖和非依赖途径上调细胞因子和趋化因子的表达。与 DIO 小鼠的皮下脂肪组织相比，肥胖诱导的大多数 TLR 基因和相关促炎信号级联在附睾脂肪组织中的上调程度更大。此外，DIO 小鼠内脏脂肪组织中 TLR1、TLR4、TLR5、TLR8、TLR9 和 TLR12 基因以及大多数下游信号分子和靶细胞因子基因的肥胖诱导上调幅度大于 ob/ob 小鼠。这些结果表明，在增大的脂肪组织中过度表达的 TLR 及其相关促炎信号分子可能在肥胖相关的代谢性炎症现象中发挥重要作用。
