Metabolism-Associated Molecular Patterns (MAMPs).

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. The pathogenesis and development of metabolic diseases are largely affected by metabolic inflammation, or 'metaflammation,' which is induced by metabolism-related danger signal molecules derived from metabolic overload. We define molecules derived from excess nutrients and their metabolites, capable of inciting inflammation via activating pattern recognition receptors (PRRs), as metabolism-associated molecular patterns (MAMPs), which are a subset of damage-associated molecular pattern (DAMPs) awaiting specific classification. MAMPs interact with PRRs to incite proinflammatory signaling pathways, such as NF-κB, MAPKs, and NLRP3 inflammasome pathways, driving the production of proinflammatory mediators and contributing to the initiation and progression of metabolic diseases. Targeting MAMPs and their downstream signaling molecules might be a promising strategy for developing therapeutic approaches to metabolic diseases. [ABSTRACT FROM AUTHOR]