Haneklaus Moritz, O'Neill Luke A J
School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Immunol Rev. 2015 May;265(1):53-62. doi: 10.1111/imr.12285.
The discovery of the NLRP3 (NLR family, pyrin domain containing 3) inflammasome provided an important molecular mechanism in the induction of the central pro-inflammatory cytokine interleukin-1β (IL-1β), via activation of caspase-1, which processes pro-IL-1β into its mature active form. IL-1 has long been known to exert metabolic effects, most notably being implicated in insulin resistance and obesity. A key phenotype of the NLRP3-deficient mouse is insulin hypersensitivity. Over the past 5 years, a number of discoveries have been made suggesting a close interplay between NLRP3 and metabolism. Metabolic products have been shown to activate NLPR3, and disturbed mitochondria have been shown to be involved in NLRP3 function. It is possible that under normal physiology NLRP3 is homeostatic and maintains the metabolic balance. However, upon chronic activation (e.g. in obesity or hypercholesterolemia), NLRP3 becomes pathologic and promotes disease. Here, we review these findings and place them in the context of exciting new insights that are improving our understanding of the link between inflammation and metabolism. These insights are giving rise to better understanding of disease pathogenesis and might point to new therapeutic approaches.
NLRP3（NLR家族含pyrin结构域蛋白3）炎性小体的发现为通过激活半胱天冬酶-1诱导促炎细胞因子白细胞介素-1β（IL-1β）提供了重要的分子机制，半胱天冬酶-1可将前体IL-1β加工成其成熟的活性形式。长期以来，人们一直知道IL-1具有代谢作用，最显著的是与胰岛素抵抗和肥胖有关。NLRP3基因缺陷小鼠的一个关键表型是胰岛素超敏反应。在过去5年里，有许多发现表明NLRP3与代谢之间存在密切的相互作用。代谢产物已被证明可激活NLRP3，而线粒体功能紊乱也被证明与NLRP3功能有关。在正常生理状态下，NLRP3可能具有稳态作用并维持代谢平衡。然而，在慢性激活时（如在肥胖或高胆固醇血症中），NLRP3会变得病理性并促进疾病发展。在此，我们回顾这些发现，并将其置于令人兴奋的新见解的背景下，这些见解正在增进我们对炎症与代谢之间联系的理解。这些见解有助于更好地理解疾病发病机制，并可能指向新的治疗方法。
