Targeting the NLRP3 inflammasome–IL-1β pathway in type 2 diabetes and obesity – published online 04/11/2024

Daniel T. Meier, Joyce de Paula Souza, Marc Y. Donath

Increased body weight is associated with chronic low-grade inflammation, which contributes to the development and complications of diabetes. Central to this pathology is the activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome complex and secretion of IL-1β and IL-18. In this issue, Meier et al (https://doi.org/10.1007/s00125-024-06306-1) describe the activation of the NLRP3 inflammasome by metabolic stress, including the molecular mechanisms involved, and discuss the consequences for tissue integrity and energy metabolism. The emerging role of IL-1β in physiology and insulin secretion is compared with the apparent pathological features of inflammation. The authors outline the potential benefits of blocking the IL-1 pathway, with a focus on the comorbidities of diabetes, but also other associated diseases such as obesity, Alzheimer’s disease, rheumatoid arthritis and gout. The authors conclude by considering the safety aspects of IL-1 antagonism, as well as the prospect of using this therapeutic approach for the treatment of type 2 diabetes. The figures from this review are available as a downloadable slideset.