Steinberg Gregory R, Schertzer Jonathan D
1] Faculty of Health Sciences, Department of Medicine, McMaster University, Hamilton, Ontario, Canada [2] Faculty of Health Sciences, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
1] Faculty of Health Sciences, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada [2] Faculty of Health Sciences, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Immunol Cell Biol. 2014 Apr;92(4):340-5. doi: 10.1038/icb.2014.11. Epub 2014 Mar 18.
Metabolic inflammation, a low-grade chronic pro-inflammatory environment in metabolic or vascular tissues during nutrient excess, has emerged as an important factor underpinning the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Macrophages are a primary source of inflammatory effectors that contribute to insulin resistance and atherosclerosis, the precursors of T2D and CVD, respectively. Oxidative metabolism dictates the inflammatory status of macrophages, effects that may be upstream of endoplasmic reticulum (ER) stress and the NLRP3 inflammasome. The AMP-activated protein kinase (AMPK) lies at the crossroads of metabolically driven macrophage inflammation and exerts control over mitochondrial metabolism, and therefore is vital for dictating the inflammatory status of macrophages. Understanding how AMPK regulates oxidative metabolism and substrate selection to control both ER stress and NLRP3 inflammasome-mediated inflammation holds promise for identifying new therapies and the tailoring of current therapies for the treatment of T2D and CVD.
代谢性炎症是营养过剩时代谢或血管组织中的一种低度慢性促炎环境，已成为2型糖尿病（T2D）和心血管疾病（CVD）发生发展的重要因素。巨噬细胞是炎症效应分子的主要来源，分别导致胰岛素抵抗和动脉粥样硬化，而胰岛素抵抗和动脉粥样硬化分别是T2D和CVD的先兆。氧化代谢决定巨噬细胞的炎症状态，其作用可能在内质网（ER）应激和NLRP3炎性小体的上游。AMP激活的蛋白激酶（AMPK）处于代谢驱动的巨噬细胞炎症的交叉点，对线粒体代谢发挥控制作用，因此对于决定巨噬细胞的炎症状态至关重要。了解AMPK如何调节氧化代谢和底物选择以控制ER应激和NLRP3炎性小体介导的炎症，有望为识别新疗法以及为T2D和CVD的治疗量身定制现有疗法提供依据。
