{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:48:22Z","timestamp":1786114102293,"version":"build-2736575974"},"reference-count":110,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medicinal Research Reviews"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chronic low\u2010grade inflammation driven by persistent NLRP3 inflammasome activation is a unifying pathophysiological feature of most non\u2010communicable diseases (NCDs). Whereas single\u2010target pharmacological inhibitors exhibit limited breadth and durability, regular moderate\u2010intensity exercise confers robust multi\u2010system protection through a diverse network of exerkines. This narrative review synthesizes evidence that exercise\u2010released myokines (irisin, Metrnl, context\u2010reprogrammed IL\u20106), hepatokines\/adipokines (FGF21, adropin, adiponectin), metabolites (lactate, \u03b2\u2010hydroxybutyrate), microbiota\u2010derived factors (SCFAs, betulinic acid), and extracellular vesicle (EV)\u2010delivered non\u2010coding RNAs converge on every regulatory node of the canonical NLRP3 inflammasome to achieve multi\u2010nodal suppression that is currently unmatched by any single pharmacological approach based on available evidence. Acute high\u2010intensity exercise transiently activates NLRP3 via canonical danger signals, whereas chronic moderate\u2010intensity training (150\u2013300\u2009min\u00b7wk\n                    <jats:sup>\u22121<\/jats:sup>\n                    , 60%\u201375% HRmax) induces profound basal suppression through NF\u2010\u03baB attenuation, mitochondrial protection, direct interference with NEK7\u2010NLRP3 interaction and ASC oligomerization, post\u2010transcriptional silencing, and enhanced autophagic clearance. These mechanisms are supported by preclinical structural data and human biomarker studies across cardiovascular, metabolic, neurodegenerative, and musculoskeletal disorders. We propose a precision exercise medicine framework integrating exerkine\/genetic\/microbiome profiling to minimize non\u2010responders, together with emerging mimetics, RNA therapeutics, and synergistic pharmacology, to deliver scalable systems\u2010level modification of NLRP3\u2010driven metaflammation.\n                  <\/jats:p>","DOI":"10.1002\/med.70063","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T04:51:36Z","timestamp":1779771096000},"page":"1455-1472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exercise\u2010Induced Exerkines: Multi\u2010Nodal Suppression of the NLRP3 Inflammasome and Translational Potential"],"prefix":"10.1002","volume":"46","author":[{"given":"Huaiming","family":"Wang","sequence":"first","affiliation":[{"name":"School of Sports Training Tianjin University of Sport Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongqiang","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Sports Training Tianjin University of Sport Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijing","family":"Di","sequence":"additional","affiliation":[{"name":"School of Physical Education Tianjin University of Sport Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Alizadeh","sequence":"additional","affiliation":[{"name":"Division of Exercise Physiology and Metabolism, Faculty of Sports Sciences The University of Mazandaran Babolsar Mazandaran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijnurstu.2023.104563"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00021.2024"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252312941"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/sms.12581"},{"key":"e_1_2_11_6_1","volume-title":"Essential Aspects of Immunometabolism in Health and Disease","author":"Batatinha H.","year":"2021"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01954-6"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00054.2021"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00641-2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4063562"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2025.04.007"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14432"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo15010059"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0336395"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2025.103057"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05570-8"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.565924"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02264-1"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00687-0"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1624770"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.04.032"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.70213"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02280-x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01177-2"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-025-05283-2"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/00368504251337526"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.14089"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2021.106013"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.591803"},{"key":"e_1_2_11_30_1","first-page":"1","article-title":"Non\u2010Pyroptotic Caspase\u201011 Activity Regulates Osteoclastogenesis and Pathological Bone Loss","author":"Piao X.","year":"2025","journal-title":"Cell Death and Differentiation"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-025-11166-y"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2024.117491"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14134606"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-69764-y"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology14010071"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.109941"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2025.115167"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26199715"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.4.1411"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fspor.2025.1602208"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2025.119227"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1987149"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55040105"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.828020"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5809298"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1249\/JES.0000000000000183"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1711656"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101167"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/os.14365"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.17267"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.792859"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70061"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2124230"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10123480"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4536470"},{"key":"e_1_2_11_56_1","first-page":"161","article-title":"Effects of High\u2010Intensity Interval vs. Moderate\u2010Intensity Continuous Training on Body Composition and Gene Expression of ACE2, NLRP3, and FNDC5 in Obese Adults: A Randomized Controlled Trial","volume":"36","author":"Armannia F.","year":"2022","journal-title":"Medical Journal of the Islamic Republic of Iran"},{"key":"e_1_2_11_57_1","unstructured":"S. H.Soleimani A. A.Daloii A.Abdi S. Z.Bouri et al.The Effect of Six Weeks of Aerobic Exercise on the Expression of Genes Involved in Aortic Tissue Pyroptosis of Healthy and Diabetic Male Mice(2022)."},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12263-020-00674-0"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.319251"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16813"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30342"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120424"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001641"},{"issue":"2","key":"e_1_2_11_64_1","first-page":"289","article-title":"Effects of Exercise Preconditioning on NLRP3 and Mitochondrial Fission in Isoproterenol\u2010Induced Myocardial Infarcted Rats","volume":"32","author":"Ahmadi A.","year":"2023","journal-title":"Comparative Clinical Pathology"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-022-01874-4"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0336395"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1082050"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0343214"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0420"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1368835"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2025.2497272"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-023-01242-x"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205268"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114118"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0273527"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-025-04350-w"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-020-00508-y"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.546445"},{"issue":"7","key":"e_1_2_11_79_1","first-page":"3338","article-title":"Adiponectin Inhibits NLRP3 Inflammasome by Modulating the AMPK\u2010ROS Pathway","volume":"11","author":"Wang F.","year":"2018","journal-title":"International Journal of Clinical and Experimental Pathology"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-023-00390-4"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3804"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1665551"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1476908"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu17091463"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24033039"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.rcm2511392"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202403818"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116631"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073788"},{"key":"e_1_2_11_90_1","first-page":"6","article-title":"Interleukin\u20106 in Acute Exercise and Training: What Is the Biological Relevance?","volume":"12","author":"Fischer C. P.","year":"2002","journal-title":"Exercise Immunology Review"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304286"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01425-3"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08055-1"},{"issue":"7","key":"e_1_2_11_94_1","first-page":"e388","article-title":"Dapansutrile, an Oral Selective NLRP3 Inflammasome Inhibitor, for Treatment of Gout Flares: An Open\u2010Label, Dose\u2010Adaptive, Proof\u2010of\u2010Concept, Phase 2 Alpha Trial","volume":"2","author":"Kluck V.","year":"2020","journal-title":"Lancet Rheumatol"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000658"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-023-01765-z"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.5646\/ch.2025.31.e34"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021372"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.02.022"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0165-0"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.016"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1295-z"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25235533"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1716095115"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314635"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1371-1"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03037-1"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1454116"},{"key":"e_1_2_11_110_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03020-24"},{"key":"e_1_2_11_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2016.02.023"}],"container-title":["Medicinal Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/med.70063","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/med.70063","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/med.70063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T20:24:13Z","timestamp":1785961453000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/med.70063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":110,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/med.70063"],"URL":"https:\/\/doi.org\/10.1002\/med.70063","archive":["Portico"],"relation":{},"ISSN":["0198-6325","1098-1128"],"issn-type":[{"value":"0198-6325","type":"print"},{"value":"1098-1128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"assertion":[{"value":"2025-12-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}