Mechanisms of macrophage activation in obesity-induced insulin resistance.
Mechanisms of macrophage activation in obesity-induced insulin resistance.
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DOI：
10.1038/ncpendmet0976
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Chawla, Ajay
中科院分区：
文献类型：
--
作者：
Odegaard, Justin I.;Chawla, Ajay
关键词：
慢性炎症是肥胖诱导的胰岛素抵抗和2型糖尿病发病机制中的关键步骤。这种低度炎症是由聚集和驻留的巨噬细胞的炎性（经典）激活介导的，巨噬细胞填充代谢组织，包括脂肪组织和肝脏。这些发现导致了脂肪组织巨噬细胞的浸润和激活与肥胖诱导的胰岛素抵抗有因果关系的概念。然而，研究表明，在脂肪组织和肝脏中居住的替代活化的巨噬细胞在肥胖诱导的代谢疾病中发挥有益的功能。通过减轻组织炎症和增加肝脏和骨骼肌中的氧化代谢，交替激活的巨噬细胞减轻了肥胖小鼠的胰岛素抵抗。巨噬细胞的不同亚群参与胰岛素抵抗的促进或减弱的发现表明，控制巨噬细胞活化的途径可以潜在地靶向治疗肥胖的这些共病。因此，这篇评论的重点是刺激和机制，控制组织巨噬细胞的经典和替代激活，以及这些巨噬细胞激活程序如何调节外周组织中的胰岛素作用。巨噬细胞活化的功能重要性进一步讨论的背景下，宿主防御，突出先天免疫和代谢之间的串扰。
Chronic inflammation is now recognized as a key step in the pathogenesis of obesity-induced insulin resistance and type 2 diabetes mellitus. This low-grade inflammation is mediated by the inflammatory (classical) activation of recruited and resident macrophages that populate metabolic tissues, including adipose tissue and liver. These findings have led to the concept that infiltration and activation of adipose tissue macrophages is causally linked to obesity-induced insulin resistance. Studies have shown, however, that alternatively activated macrophages taking residence in adipose tissue and liver perform beneficial functions in obesity-induced metabolic disease. By attenuating tissue inflammation and increasing oxidative metabolism in liver and skeletal muscle, alternatively activated macrophages have lessened insulin resistance in obese mice. The discovery that distinct subsets of macrophages are involved in the promotion or attenuation of insulin resistance suggests that pathways controlling macrophage activation can potentially be targeted to treat these co-morbidities of obesity. Thus, this Review focuses on the stimuli and mechanisms that control classical and alternative activation of tissue macrophages, and how these macrophage activation programs modulate insulin action in peripheral tissues. The functional importance of macrophage activation is further discussed in the context of host defense to highlight the crosstalk between innate immunity and metabolism.
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影响因子：
120.7
作者：
Flegal, KM;Carroll, MD;Johnson, CL
通讯作者：
Johnson, CL
影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
16.2
作者：
Ford, ES
通讯作者：
Ford, ES
DOI：
10.1097/01.mco.0000172571.41149.52
发表时间：
2005-07-01
影响因子：
3.1
作者：
Bouloumié, A;Curat, CA;Busse, R
通讯作者：
Busse, R
影响因子：
29
作者：
Kang, Kihwa;Reilly, Shannon M.;Lee, Chih-Hao
通讯作者：
Lee, Chih-Hao