Immuno-metabolic diseases and therapeutics: molecular mechanisms via inflammasome signaling

Abstract Inflammatory responses serve as essential defense mechanisms in living organisms, but persistent or excessive activation can contribute to the development of chronic metabolic diseases. A central regulator of such inflammation is the inflammasome, a cytosolic multiprotein complex that sense...

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Bibliographic Details
Main Author: Joo-Hui Han
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Cell Communication and Signaling
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Online Access:https://doi.org/10.1186/s12964-025-02368-9
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Summary:Abstract Inflammatory responses serve as essential defense mechanisms in living organisms, but persistent or excessive activation can contribute to the development of chronic metabolic diseases. A central regulator of such inflammation is the inflammasome, a cytosolic multiprotein complex that senses pathogenic or stress-related signals and triggers the maturation of pro-inflammatory cytokines, particularly interleukin-1β (IL-1β) and interleukin-18 (IL-18). While inflammasome-induced pyroptosis, a form of lytic cell death, can play protective roles in pathogen clearance, excessive or dysregulated activation is more commonly associated with chronic inflammation and tissue damage. Increasing evidence points to the involvement of inflammasomes, especially the NLRP3 inflammasome, in the pathogenesis of immune-metabolic diseases that characterized by the interplay between immune dysfunction and metabolic imbalance, including obesity, diabetes, atherosclerosis, and sarcopenia. In these conditions, aberrant inflammasome activity contributes to insulin resistance, lipid dysregulation, muscle wasting, and vascular injury through sustained cytokine release and immune cell recruitment. Recent studies have advanced our understanding of how inflammasome signaling is integrated into the molecular landscape of metabolic disease, offering new insights into disease mechanisms and highlighting inflammasomes as viable therapeutic targets. This review provides an updated overview of inflammasome biology, defines their role in four representative immune-metabolic diseases, and discusses recent progress in targeting inflammasome pathways as a strategy to mitigate chronic inflammation and metabolic dysfunction.
ISSN:1478-811X