Adipose tissue remodeling as homeostatic inflammation.
Adipose tissue remodeling as homeostatic inflammation.
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DOI：
10.4061/2011/720926
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发表时间：
2011
影响因子：
2
通讯作者：
Ogawa Y
中科院分区：
文献类型：
--
作者：
Itoh M;Suganami T;Hachiya R;Ogawa Y
越来越多的证据表明，肥胖与慢性、低度炎症状态有关。肥胖脂肪组织的特征在于细胞组成和功能的动态变化，其可被称为“脂肪组织重塑”。在脂肪组织中的基质细胞中，浸润的巨噬细胞在脂肪组织炎症和全身性胰岛素抵抗中起重要作用。我们已经证明，分别来自脂肪细胞和巨噬细胞的饱和脂肪酸和肿瘤坏死因子-α的旁分泌环，可抑制肥胖诱导的脂肪组织炎症。值得注意的是，通过巨噬细胞诱导的脂解从肥大的脂肪细胞释放的饱和脂肪酸充当Toll样受体4复合物的天然存在的配体，从而激活巨噬细胞。来源于实质细胞的内源性配体与在基质免疫细胞中表达的病原体传感器之间的这种持续相互作用应导致范围从基础稳态到患病组织重塑的慢性炎症反应，其可被称为“稳态炎症”。因此，我们假设脂肪组织重塑可能代表了稳态炎症的原型。了解稳态炎症的分子机制可能会导致识别新的治疗策略，以预防或治疗肥胖相关的并发症。
Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.