Macrophages, Inflammation, and Insulin Resistance

被引:2102
作者
Olefsky, Jerrold M. [1 ]
Glass, Christopher K. [1 ,2 ]
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
关键词
obesity; adipose tissue; skeletal muscle; Kupffer cell; ACTIVATED RECEPTOR-GAMMA; ADIPOSE-TISSUE INFLAMMATION; GLYCATION END-PRODUCTS; TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTORS; ENDOPLASMIC-RETICULUM STRESS; DEPENDENT DIABETES-MELLITUS; PPAR-GAMMA; FATTY-ACIDS; NUCLEAR RECEPTORS;
D O I
10.1146/annurev-physiol-021909-135846
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Obesity induces an insulin-resistant state in adipose tissue, liver, and muscle and is a strong risk factor for the development of type 2 diabetes mellitus. Insulin resistance in the setting of obesity results from a combination of altered functions of insulin target cells and the accumulation of macrophages that secrete proinflammatory mediators. At the molecular level, insulin resistance is promoted by a transition in macrophage polarization from an alternative M2 activation state maintained by STAT6 and PPA.Rs to a classical M1 activation state driven by NE-kappa B, AP1, and other signal-dependent transcription factors that play crucial roles in innate immunity. Strategies focused on inhibiting the inflammation/insulin resistance axis that otherwise preserve essential innate immune functions may hold promise for therapeutic intervention.
引用
收藏
页码:219 / 246
页数:28
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