Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Int J Environ Res Public Health. 2021 Jan 10;18(2):511. doi: 10.3390/ijerph18020511.
NLRP3 inflammasome is one of the multimeric protein complexes of the nucleotide-binding domain, leucine-rich repeat (NLR)-containing pyrin and HIN domain family (PYHIN). When activated, NLRP3 inflammasome triggers the release of pro-inflammatory interleukins (IL)-1β and IL-18, an essential step in innate immune response; however, defective checkpoints in inflammasome activation may lead to autoimmune, autoinflammatory, and metabolic disorders. Among the consequences of NLRP3 inflammasome activation is systemic chronic low-grade inflammation, a cardinal feature of obesity and insulin resistance. Understanding the mechanisms involved in the regulation of NLRP3 inflammasome in adipose tissue may help in the development of specific inhibitors for the treatment and prevention of obesity-mediated metabolic diseases. In this narrative review, the current understanding of NLRP3 inflammasome activation and regulation is highlighted, including its putative roles in adipose tissue dysfunction and insulin resistance. Specific inhibitors of NLRP3 inflammasome activation which can potentially be used to treat metabolic disorders are also discussed.
NLRP3 炎性小体是核苷酸结合域、富含亮氨酸重复序列(NLR)和含 PYHIN 域家族(PYHIN)的多聚体蛋白复合物之一。当被激活时,NLRP3 炎性小体触发促炎细胞因子(IL)-1β和 IL-18 的释放,这是先天免疫反应的重要步骤;然而,炎性小体激活中的缺陷检查点可能导致自身免疫、自身炎症和代谢紊乱。NLRP3 炎性小体激活的后果之一是全身慢性低度炎症,这是肥胖和胰岛素抵抗的一个主要特征。了解脂肪组织中 NLRP3 炎性小体调节的机制可能有助于开发用于治疗和预防肥胖介导的代谢疾病的特异性抑制剂。在这篇叙述性综述中,强调了 NLRP3 炎性小体激活和调节的当前理解,包括其在脂肪组织功能障碍和胰岛素抵抗中的推测作用。还讨论了可能用于治疗代谢紊乱的 NLRP3 炎性小体激活的特异性抑制剂。