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肥胖症中的脂肪组织炎症与代谢功能障碍。

Adipose tissue inflammation and metabolic dysfunction in obesity.

机构信息

The Cardiovascular Research Center and The Limole Center for Integrated Lymphatic Research, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.

出版信息

Am J Physiol Cell Physiol. 2021 Mar 1;320(3):C375-C391. doi: 10.1152/ajpcell.00379.2020. Epub 2020 Dec 23.

Abstract

Several lines of preclinical and clinical research have confirmed that chronic low-grade inflammation of adipose tissue is mechanistically linked to metabolic disease and organ tissue complications in the overweight and obese organism. Despite this widely confirmed paradigm, numerous open questions and knowledge gaps remain to be investigated. This is mainly due to the intricately intertwined cross-talk of various pro- and anti-inflammatory signaling cascades involved in the immune response of expanding adipose depots, particularly the visceral adipose tissue. Adipose tissue inflammation is initiated and sustained over time by dysfunctional adipocytes that secrete inflammatory adipokines and by infiltration of bone marrow-derived immune cells that signal via production of cytokines and chemokines. Despite its low-grade nature, adipose tissue inflammation negatively impacts remote organ function, a phenomenon that is considered causative of the complications of obesity. The aim of this review is to broadly present an overview of adipose tissue inflammation by highlighting the most recent reports in the scientific literature and summarizing our overall understanding of the field. We also discuss key endogenous anti-inflammatory mediators and analyze their mechanistic role(s) in the pathogenesis and treatment of adipose tissue inflammation. In doing so, we hope to stimulate studies to uncover novel physiological, cellular, and molecular targets for the treatment of obesity.

摘要

已有数条临床前和临床研究证实,脂肪组织的慢性低度炎症与超重和肥胖机体中的代谢性疾病和器官组织并发症在机制上有关联。尽管这一被广泛证实的模式已经存在,但仍有许多悬而未决的问题和知识空白需要研究。这主要是由于涉及扩张脂肪组织(特别是内脏脂肪组织)免疫反应的各种促炎和抗炎信号级联的错综复杂的相互作用。脂肪组织炎症是由功能失调的脂肪细胞分泌促炎脂肪因子以及骨髓来源的免疫细胞浸润引发的,这些细胞通过产生细胞因子和趋化因子来发出信号,并随着时间的推移而持续存在。尽管其性质为低度炎症,但脂肪组织炎症会对远程器官功能产生负面影响,这一现象被认为是肥胖并发症的原因。本综述的目的是通过强调科学文献中的最新报道,广泛介绍脂肪组织炎症的概述,并总结我们对该领域的整体理解。我们还讨论了关键的内源性抗炎介质,并分析了它们在脂肪组织炎症发病机制和治疗中的作用。希望通过这样做,能够激发研究工作,以揭示治疗肥胖症的新的生理、细胞和分子靶标。

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