{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:48:04Z","timestamp":1793303284806,"version":"4.5.0"},"reference-count":174,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018551","name":"Science and Technology Innovation Talents in Universities of Henan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018551","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The NOD-like receptor (NLR) inflammasome system is an evolutionarily conserved intracellular surveillance network that responds to pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and metabolism-associated molecular patterns (MAMPs). Beyond the well-characterized NLRP3 inflammasome, accumulating evidence suggests that NLRP1, NLRP6, NLRC5, NLRP12, and NLRP2 are also implicated in metabolic disorders, including obesity, type 2 diabetes mellitus (T2DM), atherosclerosis, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review summarizes the molecular mechanisms governing NLR inflammasome activation and discusses the divergent, context-dependent roles of selected NLR family members in metabolic inflammation. We distinguish established inflammasome-dependent pathways from emerging inflammasome-independent and PANoptosis-related mechanisms, with particular attention to species differences, disease context, and strength of evidence. Therapeutic strategies targeting inflammasome components or downstream effectors are critically evaluated, including small-molecule inhibitors, cytokine blockade, peptide-derived agents, and natural bioactive compounds. By integrating mechanistic findings with a translational evidence hierarchy spanning\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies, animal models, human observational data, early clinical trials, randomized evidence, and approved or repurposed anti-inflammatory therapies, this review highlights both the promise and limitations of precision inflammasome modulation for metabolic disease intervention, providing an evidence-graded therapeutic perspective on NLR biology in metabolic disease.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1823724","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T20:10:10Z","timestamp":1779999010000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["NLR inflammasome pathways: key targets for pathogenesis and therapy of metabolic diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"Jun","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohao","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"He","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueke","family":"Ma","sequence":"additional","affiliation":[{"name":"The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]},{"name":"The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University","place":["Xinxiang, Henan, 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