Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
Trends Endocrinol Metab. 2020 Oct;31(10):712-724. doi: 10.1016/j.tem.2020.07.001. Epub 2020 Aug 14.
Metabolic diseases pose a tremendous health threat in both developed and developing countries. The pathophysiology of metabolic diseases is complex but has been shown to be closely associated with sterile inflammation, which is initiated by various danger molecules derived from metabolic overload, such as oxidized low-density lipoproteins (OxLDLs), free fatty acids (FFAs), glucose, advanced glycation end products (AGEs), and cholesterol. These danger signals are sensed by pattern recognition receptors (PRRs) to activate proinflammatory signaling pathways and promote the release of proinflammatory mediators, leading to chronic low-grade inflammation. Although these harmful metabolic stimuli are generally regarded as damage-associated molecular patterns (DAMPs), a more specific definition and accurate classification for these DAMPs is still missing. In this opinion, we classify the harmful metabolic stimuli that can incite inflammatory responses and tissue damage via instigating PRRs as metabolism-associated molecular patterns (MAMPs), and we summarize their roles in metaflammation-mediated metabolic diseases.
代谢性疾病在发达国家和发展中国家都构成了巨大的健康威胁。代谢性疾病的病理生理学非常复杂,但已被证明与无菌炎症密切相关,无菌炎症是由代谢超负荷产生的各种危险分子引发的,如氧化型低密度脂蛋白(OxLDLs)、游离脂肪酸(FFAs)、葡萄糖、晚期糖基化终产物(AGEs)和胆固醇。这些危险信号被模式识别受体(PRRs)感知,激活促炎信号通路并促进促炎介质的释放,导致慢性低度炎症。尽管这些有害的代谢刺激通常被认为是损伤相关分子模式(DAMPs),但对于这些 DAMPs 还缺乏更具体的定义和准确的分类。在本观点中,我们将能够通过引发 PRRs 引发炎症反应和组织损伤的有害代谢刺激物分类为代谢相关分子模式(MAMPs),并总结它们在代谢炎症介导的代谢性疾病中的作用。