{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:07:32Z","timestamp":1787065652528,"version":"build-2736575974"},"reference-count":212,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Iron is essential for cellular respiration, oxidative defense, and host immunity, but its dysregulation is increasingly associated with metabolic disorders, such as obesity and type 2 diabetes. In these diseases, regional iron accumulation occurs in adipose tissue, independent of systemic overload. This process disrupts the mitochondrial redox balance, induces ferroptotic stress, and activates the innate immune pathways. Recent studies have highlighted the NLRP3 (nucleotide-binding domain, leucine-rich repeat, pyrin domain-containing protein 3) inflammasome and its effector cytokine interleukin-1\u03b2 (IL-1\u03b2) as important mediators of the interface between iron and inflammation. In both adipocytes and macrophages, labile iron increased reactive oxygen species (ROS) production and promoted inflammasome formation. Simultaneously, metabolic stress factors upregulate hepcidin expression, suppress ferroportin activity and exacerbate intracellular iron retention. These molecular events converge to maintain low-grade inflammation and impair insulin signaling. Despite these compelling associations, direct mechanistic evidence remains limited, particularly with respect to depot-specific responses and cell type resolution. In this review, I examine the current evidence linking iron handling and inflammasome biology in adipose tissue, focusing on ferroptosis, thioredoxin-interacting protein (TXNIP) signaling, and spatial mapping of iron\u2013cytokine networks. I also discuss novel therapeutic strategies targeting iron overload and inflammasome activation, including chelation, hepcidin modulation, and inflammasome inhibition in the context of metabolic diseases.<\/jats:p>","DOI":"10.3390\/ijms26178304","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:31:12Z","timestamp":1756373472000},"page":"8304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Iron\u2013Inflammasome Crosstalk in Adipose Tissue: Unresolved Roles of NLRP3 and IL-1\u03b2 in Metabolic Inflammation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2374-4462","authenticated-orcid":false,"given":"Sixtus","family":"Aguree","sequence":"first","affiliation":[{"name":"Department of Applied Health Science, Indiana University School of Public Health, Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Diabetes Collaborators (2023). 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