{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T21:03:44Z","timestamp":1781211824995,"version":"3.54.1"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Metabolism Open"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.metop.2026.100466","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T07:56:56Z","timestamp":1775721416000},"page":"100466","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Bridging exercise biology and immunometabolism: A novel irisin pathway toward next-generation metabolic and neurodegenerative therapies"],"prefix":"10.1016","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7008-388X","authenticated-orcid":false,"given":"Maria","family":"Dalamaga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"7382","key":"10.1016\/j.metop.2026.100466_bib1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Bostr\u00f6m","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.metop.2026.100466_bib2","article-title":"Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells","volume":"3","author":"Mu","year":"2026","journal-title":"Nat Metab"},{"issue":"2","key":"10.1016\/j.metop.2026.100466_bib3","doi-asserted-by":"crossref","first-page":"514","DOI":"10.2337\/db13-1106","article-title":"Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling","volume":"63","author":"Zhang","year":"2014","journal-title":"Diabetes"},{"issue":"3","key":"10.1016\/j.metop.2026.100466_bib4","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s44321-024-00027-z","article-title":"Exerkines and cardiometabolic benefits of exercise: from bench to clinic","volume":"16","author":"Jin","year":"2024","journal-title":"EMBO Mol Med"},{"issue":"Pt 2","key":"10.1016\/j.metop.2026.100466_bib5","article-title":"Myokine-mediated muscle-organ interactions: molecular mechanisms and clinical significance","volume":"242","author":"Yi","year":"2025","journal-title":"Biochem Pharmacol"},{"issue":"3","key":"10.1016\/j.metop.2026.100466_bib6","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/ni.3085","article-title":"The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells","volume":"16","author":"Vasanthakumar","year":"2015","journal-title":"Nat Immunol"},{"issue":"2","key":"10.1016\/j.metop.2026.100466_bib7","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cmet.2023.12.019","article-title":"Niche-specific control of tissue function by regulatory T cells-current challenges and perspectives for targeting metabolic disease","volume":"36","author":"Becker","year":"2024","journal-title":"Cell Metab"},{"issue":"6","key":"10.1016\/j.metop.2026.100466_bib8","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.immuni.2024.04.002","article-title":"Adipose-tissue treg cells restrain differentiation of stromal adipocyte precursors to promote insulin sensitivity and metabolic homeostasis","volume":"57","author":"Wang","year":"2024","journal-title":"Immunity"},{"issue":"10","key":"10.1016\/j.metop.2026.100466_bib9","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.4049\/jimmunol.1500020","article-title":"IL-33 reverses an obesity-induced deficit in visceral adipose tissue ST2+ T regulatory cells and ameliorates adipose tissue inflammation and insulin resistance","volume":"194","author":"Han","year":"2015","journal-title":"J Immunol"},{"issue":"6","key":"10.1016\/j.metop.2026.100466_bib10","doi-asserted-by":"crossref","first-page":"H1387","DOI":"10.1152\/ajpheart.00491.2020","article-title":"Interleukin-33 rescues perivascular adipose tissue anticontractile function in obesity","volume":"319","author":"Saxton","year":"2020","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.metop.2026.100466_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.176059","article-title":"IL-33 promotes pancreatic \u03b2-cell survival and insulin secretion under diabetogenic conditions through PPAR\u03b3","volume":"959","author":"Lin","year":"2023","journal-title":"Eur J Pharmacol"},{"issue":"5","key":"10.1016\/j.metop.2026.100466_bib12","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.immuni.2017.10.015","article-title":"Interleukin-33-Activated islet-resident innate lymphoid cells promote insulin secretion through myeloid cell retinoic acid production","volume":"47","author":"Dalmas","year":"2017","journal-title":"Immunity"},{"key":"10.1016\/j.metop.2026.100466_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2025.112455","article-title":"Dynamic regulation of IL-33 in the obesity pathogenesis: spatiotemporal specificity and functional paradoxes","volume":"229","author":"Cui","year":"2025","journal-title":"Diabetes Res Clin Pract"},{"issue":"Pt A","key":"10.1016\/j.metop.2026.100466_bib14","article-title":"Effects of IL-33 on 3T3-L1 cells and Obese mice models induced by a high-fat diet","volume":"101","author":"Kai","year":"2021","journal-title":"Int Immunopharmacol"},{"issue":"11","key":"10.1016\/j.metop.2026.100466_bib15","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1038\/s41366-025-01873-8","article-title":"Interleukin-33 promotes lipolysis of adipocytes and protects male mice against obesity via activation of \u03b2-adrenergic receptor signaling","volume":"49","author":"Chen","year":"2025","journal-title":"Int J Obes"},{"issue":"21","key":"10.1016\/j.metop.2026.100466_bib16","doi-asserted-by":"crossref","first-page":"9765","DOI":"10.1073\/pnas.0908771107","article-title":"Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob\/ob mice","volume":"107","author":"Ilan","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"10.1016\/j.metop.2026.100466_bib17","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1038\/s41467-025-57918-z","article-title":"Regulatory T cells in the mouse hypothalamus control immune activation and ameliorate metabolic impairments in high-calorie environments","volume":"16","author":"Becker","year":"2025","journal-title":"Nat Commun"},{"issue":"7580","key":"10.1016\/j.metop.2026.100466_bib18","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/nature16151","article-title":"Depletion of fat-resident Treg cells prevents age-associated insulin resistance","volume":"528","author":"Bapat","year":"2015","journal-title":"Nature"},{"issue":"8","key":"10.1016\/j.metop.2026.100466_bib19","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20191542","article-title":"T reg-specific insulin receptor deletion prevents diet-induced and age-associated metabolic syndrome","volume":"217","author":"Wu","year":"2020","journal-title":"J Exp Med"},{"issue":"2","key":"10.1016\/j.metop.2026.100466_bib20","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.bbrc.2019.08.112","article-title":"Recombinant irisin induces weight loss in high fat DIO mice through increase in energy consumption and thermogenesis","volume":"519","author":"Niranjan","year":"2019","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.metop.2026.100466_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2020.110915","article-title":"Involvement of the p62\/Nrf2\/HO-1 pathway in the browning effect of irisin in 3T3-L1 adipocytes","volume":"514","author":"Tsai","year":"2020","journal-title":"Mol Cell Endocrinol"},{"issue":"16","key":"10.1016\/j.metop.2026.100466_bib22","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.jacc.2025.06.055","article-title":"The adipokine hypothesis of heart failure with a preserved ejection fraction: a novel framework to explain pathogenesis and guide treatment","volume":"86","author":"Packer","year":"2025","journal-title":"J Am Coll Cardiol"},{"issue":"9","key":"10.1016\/j.metop.2026.100466_bib23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0073680","article-title":"Evidence against a beneficial effect of irisin in humans","volume":"8","author":"Raschke","year":"2013","journal-title":"PLoS One"},{"issue":"4","key":"10.1016\/j.metop.2026.100466_bib24","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1210\/endrev\/bnab003","article-title":"Progress and challenges in the biology of FNDC5 and irisin","volume":"42","author":"Maak","year":"2021","journal-title":"Endocr Rev"},{"issue":"9","key":"10.1016\/j.metop.2026.100466_bib25","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.tem.2022.06.003","article-title":"Irisin, a fascinating field in our times","volume":"33","author":"Bao","year":"2022","journal-title":"Trends Endocrinol Metabol"},{"issue":"1","key":"10.1016\/j.metop.2026.100466_bib26","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12020-018-1550-3","article-title":"Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors","volume":"61","author":"Stratigou","year":"2018","journal-title":"Endocrine"},{"issue":"3","key":"10.1016\/j.metop.2026.100466_bib27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3390\/biom14030291","article-title":"Alterations of the adipo-myokine irisin in sepsis and septic shock: diagnostic and prognostic implications","volume":"14","author":"Karampela","year":"2024","journal-title":"Biomolecules"},{"issue":"12","key":"10.1016\/j.metop.2026.100466_bib28","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/j.metabol.2013.09.007","article-title":"Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome","volume":"62","author":"Dalamaga","year":"2013","journal-title":"Metabolism"},{"issue":"4","key":"10.1016\/j.metop.2026.100466_bib29","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.maturitas.2008.03.012","article-title":"Leptin, soluble leptin receptor, adiponectin and resistin in relation to OGTT in overweight\/obese postmenopausal women","volume":"59","author":"Hroussalas","year":"2008","journal-title":"Maturitas"},{"key":"10.1016\/j.metop.2026.100466_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2024.123225","article-title":"Exercise, exerkines and exercise mimetic drugs: molecular mechanisms and therapeutics","volume":"359","author":"Samant","year":"2024","journal-title":"Life Sci"},{"issue":"3","key":"10.1016\/j.metop.2026.100466_bib31","doi-asserted-by":"crossref","first-page":"674","DOI":"10.2337\/db16-0843","article-title":"Inorganic nitrate mimics exercise-stimulated muscular fiber-type switching and myokine and \u03b3-Aminobutyric acid release","volume":"66","author":"Roberts","year":"2017","journal-title":"Diabetes"},{"issue":"1","key":"10.1016\/j.metop.2026.100466_bib32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s13679-025-00612-4","article-title":"The many facets of PPAR-\u03b3 agonism in obesity and associated comorbidities: benefits, risks, challenges, and future directions","volume":"14","author":"Kounatidis","year":"2025","journal-title":"Curr Obes Rep"},{"issue":"5","key":"10.1016\/j.metop.2026.100466_bib33","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","article-title":"Exercise induces hippocampal BDNF through a PGC-1\u03b1\/FNDC5 pathway","volume":"18","author":"Wrann","year":"2013","journal-title":"Cell Metab"},{"issue":"1","key":"10.1016\/j.metop.2026.100466_bib34","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41591-018-0275-4","article-title":"Exercise-linked FNDC5\/irisin rescues synaptic plasticity and memory defects in Alzheimer's models","volume":"25","author":"Lourenco","year":"2019","journal-title":"Nat Med"},{"issue":"22","key":"10.1016\/j.metop.2026.100466_bib35","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1016\/j.neuron.2023.08.012","article-title":"Irisin reduces amyloid-\u03b2 by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling","volume":"111","author":"Kim","year":"2023","journal-title":"Neuron"},{"issue":"36","key":"10.1016\/j.metop.2026.100466_bib36","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2204835119","article-title":"Amelioration of pathologic \u03b1-synuclein-induced parkinson's disease by irisin","volume":"119","author":"Kam","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.metop.2026.100466_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.metop.2023.100233","article-title":"Could exercise hormone irisin be a therapeutic agent against Parkinson's and other neurodegenerative diseases?","volume":"17","author":"Avgerinos","year":"2023","journal-title":"Metabol Open"},{"issue":"1","key":"10.1016\/j.metop.2026.100466_bib38","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1186\/s12967-022-03570-w","article-title":"Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation","volume":"20","author":"Rao","year":"2022","journal-title":"J Transl Med"},{"issue":"19","key":"10.1016\/j.metop.2026.100466_bib39","doi-asserted-by":"crossref","first-page":"E2705","DOI":"10.1073\/pnas.1604032113","article-title":"IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline","volume":"113","author":"Fu","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"10.1016\/j.metop.2026.100466_bib40","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/s12974-020-01939-6","article-title":"Hippocampal interleukin-33 mediates neuroinflammation-induced cognitive impairments","volume":"17","author":"Reverchon","year":"2020","journal-title":"J Neuroinflammation"},{"issue":"1","key":"10.1016\/j.metop.2026.100466_bib41","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12933-023-01765-z","article-title":"Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial","volume":"22","author":"Sandsdal","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"10.1016\/j.metop.2026.100466_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.metop.2026.100449","article-title":"GLP-1 receptor agonists and obstructive lung disease: beyond metabolic control to respiratory outcomes","volume":"29","author":"Georgakopoulou","year":"2026","journal-title":"Metabol Open"},{"key":"10.1016\/j.metop.2026.100466_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.metop.2026.100463","article-title":"Obesity pharmacotherapy reimagined: the era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies","volume":"30","author":"Lempesis","year":"2026","journal-title":"Metabolism Open"},{"issue":"2","key":"10.1016\/j.metop.2026.100466_bib44","doi-asserted-by":"crossref","DOI":"10.1111\/sji.70095","article-title":"Immunotherapy for type 2 diabetes: mechanisms and therapeutic advances","volume":"103","author":"Sanjai","year":"2026","journal-title":"Scand J Immunol"},{"key":"10.1016\/j.metop.2026.100466_bib45","first-page":"1","article-title":"Natural constituents from food sources as therapeutic agents for obesity and metabolic diseases targeting adipose tissue inflammation","volume":"28","author":"Li","year":"2020","journal-title":"Crit Rev Food Sci Nutr"},{"issue":"4","key":"10.1016\/j.metop.2026.100466_bib46","doi-asserted-by":"crossref","DOI":"10.1111\/obr.70046","article-title":"Meteorin-like protein (metrnl): an exercise-induced myokine with therapeutic potential in metabolic and inflammatory disorders","volume":"27","author":"Zhou","year":"2026","journal-title":"Obes Rev"},{"issue":"1","key":"10.1016\/j.metop.2026.100466_bib47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1507\/endocrj.EJ21-0294","article-title":"Elucidating exercise-induced skeletal muscle signaling pathways and applying relevant findings to preemptive therapy for lifestyle-related diseases","volume":"69","author":"Iwabu","year":"2022","journal-title":"Endocr J"},{"issue":"2","key":"10.1016\/j.metop.2026.100466_bib48","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0211568","article-title":"Pharmacological AMPK activation induces transcriptional responses congruent to exercise in skeletal and cardiac muscle, adipose tissues and liver","volume":"14","author":"Muise","year":"2019","journal-title":"PLoS One"},{"issue":"15","key":"10.1016\/j.metop.2026.100466_bib49","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1056\/NEJMcibr1900041","article-title":"Boning up on irisin","volume":"380","author":"Farmer","year":"2019","journal-title":"N Engl J Med"},{"issue":"11","key":"10.1016\/j.metop.2026.100466_bib50","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/s41573-021-00217-1","article-title":"Exercise mimetics: harnessing the therapeutic effects of physical activity","volume":"20","author":"Gubert","year":"2021","journal-title":"Nat Rev Drug Discov"}],"container-title":["Metabolism Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589936826000253?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589936826000253?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:17:18Z","timestamp":1781209038000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589936826000253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":50,"alternative-id":["S2589936826000253"],"URL":"https:\/\/doi.org\/10.1016\/j.metop.2026.100466","relation":{},"ISSN":["2589-9368"],"issn-type":[{"value":"2589-9368","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bridging exercise biology and immunometabolism: A novel irisin pathway toward next-generation metabolic and neurodegenerative therapies","name":"articletitle","label":"Article Title"},{"value":"Metabolism Open","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.metop.2026.100466","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"100466"}}