{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:50:03Z","timestamp":1791597003244,"version":"4.3.4"},"reference-count":48,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["20212ACB206012"],"award-info":[{"award-number":["20212ACB206012"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020205","name":"Jiangxi Province Health Commission","doi-asserted-by":"publisher","award":["20202BCD42013"],"award-info":[{"award-number":["20202BCD42013"]}],"id":[{"id":"10.13039\/501100020205","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460077"],"award-info":[{"award-number":["82460077"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060017"],"award-info":[{"award-number":["82060017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.isci.2026.117420","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:34:44Z","timestamp":1788881684000},"page":"117420","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise-induced adipose tissue ADRB2-PGC1\u03b1-FGF21 signaling protects against pathological cardiac hypertrophy"],"prefix":"10.1016","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9734-7955","authenticated-orcid":false,"given":"Feng","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruichun","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2026.117420_bib1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41580-021-00350-0","article-title":"The cellular and functional complexity of thermogenic fat","volume":"22","author":"Cohen","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2026.117420_bib2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1172\/JCI62308","article-title":"Brown adipose tissue regulates glucose homeostasis and insulin sensitivity","volume":"123","author":"Stanford","year":"2013","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.isci.2026.117420_bib3","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.cell.2014.03.066","article-title":"Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat","volume":"157","author":"Qiu","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.isci.2026.117420_bib4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1210\/endrev\/bnac015","article-title":"Brown Adipose Tissue-A Translational Perspective","volume":"44","author":"Carpentier","year":"2023","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.isci.2026.117420_bib5","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev-physiol-021113-170252","article-title":"A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis","volume":"76","author":"Kajimura","year":"2014","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.isci.2026.117420_bib6","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev-nutr-071813-105330","article-title":"The Ontogeny of Brown Adipose Tissue","volume":"35","author":"Symonds","year":"2015","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.isci.2026.117420_bib7","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.isci.2026.117420_bib8","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1002\/oby.21124","article-title":"Anti-obesity and metabolic efficacy of the \u03b23-adrenergic agonist, CL316243, in mice at thermoneutrality compared to 22\u00b0C","volume":"23","author":"Xiao","year":"2015","journal-title":"Obesity (Silver Spring)"},{"key":"10.1016\/j.isci.2026.117420_bib9","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23094759","article-title":"Many Ways to Rome: Exercise, Cold Exposure and Diet-Do They All Affect BAT Activation and WAT Browning in the Same Manner?","volume":"23","author":"Scheel","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.117420_bib10","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cmet.2005.05.004","article-title":"Metabolic control through the PGC-1 family of transcription coactivators","volume":"1","author":"Lin","year":"2005","journal-title":"Cell Metab."},{"key":"10.1016\/j.isci.2026.117420_bib11","doi-asserted-by":"crossref","first-page":"21401","DOI":"10.1073\/pnas.0909131106","article-title":"The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle","volume":"106","author":"Chinsomboon","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117420_bib12","article-title":"Thermogenesis and Energy Metabolism in Brown Adipose Tissue in Animals Experiencing Cold Stress","volume":"26","author":"Zhang","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.117420_bib13","doi-asserted-by":"crossref","first-page":"9635","DOI":"10.1073\/pnas.1207287109","article-title":"Development of insulin resistance in mice lacking PGC-1\u03b1 in adipose tissues","volume":"109","author":"Kleiner","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117420_bib14","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.nutres.2012.06.020","article-title":"Endurance training blocks uncoupling protein 1 up-regulation in brown adipose tissue while increasing uncoupling protein 3 in the muscle tissue of rats fed with a high-sugar diet","volume":"32","author":"de Queiroz","year":"2012","journal-title":"Nutr. Res."},{"key":"10.1016\/j.isci.2026.117420_bib15","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/0031-9384(94)00005-P","article-title":"Exercise-training reduces BAT thermogenesis in rats","volume":"57","author":"Larue-Achagiotis","year":"1995","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.isci.2026.117420_bib16","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0047-6374(96)01727-7","article-title":"Swimming training improves brown-adipose-tissue activity in young and old mice","volume":"89","author":"Oh-ishi","year":"1996","journal-title":"Mech. Ageing Dev."},{"key":"10.1016\/j.isci.2026.117420_bib17","doi-asserted-by":"crossref","first-page":"34129","DOI":"10.1074\/jbc.M114.591008","article-title":"Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure","volume":"289","author":"Wu","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2026.117420_bib18","doi-asserted-by":"crossref","DOI":"10.1080\/21623945.2023.2266147","article-title":"Regulatory effects and mechanisms of exercise on activation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT)","volume":"12","author":"Dong","year":"2023","journal-title":"Adipocyte"},{"key":"10.1016\/j.isci.2026.117420_bib19","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.3390\/ijms26052136","article-title":"Molecular Mechanism of Aerobic Exercise Ameliorating Myocardial Mitochondrial Injury in Mice with Heart Failure","volume":"26","author":"Jia","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.117420_bib20","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.123.010569","article-title":"Aerobic Exercise Attenuates Pressure Overload-Induced Myocardial Remodeling and Myocardial Inflammation via Upregulating miR-574-3p in Mice","volume":"17","author":"Chen","year":"2024","journal-title":"Circ. Heart Fail."},{"key":"10.1016\/j.isci.2026.117420_bib21","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1002\/jcp.30342","article-title":"Aerobic exercise ameliorates cardiac hypertrophy by regulating mitochondrial quality control and endoplasmic reticulum stress through M(2) AChR","volume":"236","author":"Ma","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.isci.2026.117420_bib22","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1161\/CIRCULATIONAHA.120.047000","article-title":"Antihypertrophic Memory After Regression of Exercise-Induced Physiological Myocardial Hypertrophy Is Mediated by the Long Noncoding RNA Mhrt779","volume":"143","author":"Lin","year":"2021","journal-title":"Circulation"},{"key":"10.1016\/j.isci.2026.117420_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2020.154396","article-title":"UCP1-dependent and UCP1-independent metabolic changes induced by acute cold exposure in brown adipose tissue of mice","volume":"113","author":"Okamatsu-Ogura","year":"2020","journal-title":"Metabolism."},{"key":"10.1016\/j.isci.2026.117420_bib24","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1210\/en.2006-1646","article-title":"An increase in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by beta-adrenergic receptor activation","volume":"148","author":"Miura","year":"2007","journal-title":"Endocrinology"},{"key":"10.1016\/j.isci.2026.117420_bib25","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1161\/CIRCRESAHA.115.306961","article-title":"Differential Role of G Protein-Coupled Receptor Kinase 5 in Physiological Versus Pathological Cardiac Hypertrophy","volume":"117","author":"Traynham","year":"2015","journal-title":"Circ. Res."},{"key":"10.1016\/j.isci.2026.117420_bib26","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1161\/CIRCRESAHA.121.320458","article-title":"Small Extracellular Vesicles From Brown Adipose Tissue Mediate Exercise Cardioprotection","volume":"130","author":"Zhao","year":"2022","journal-title":"Circ. Res."},{"key":"10.1016\/j.isci.2026.117420_bib27","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.cmet.2018.06.013","article-title":"A(2A) Receptor Activation Attenuates Hypertensive Cardiac Remodeling via Promoting Brown Adipose Tissue-Derived FGF21","volume":"28","author":"Ruan","year":"2018","journal-title":"Cell Metab."},{"key":"10.1016\/j.isci.2026.117420_bib28","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1038\/ncomms3019","article-title":"Fibroblast growth factor 21 protects against cardiac hypertrophy in mice","volume":"4","author":"Planavila","year":"2013","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117420_bib29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jshs.2022.10.003","article-title":"Exercise sustains the hallmarks of health","volume":"12","author":"Qiu","year":"2023","journal-title":"J. Sport Health Sci."},{"key":"10.1016\/j.isci.2026.117420_bib30","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.cmet.2013.06.003","article-title":"Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis","volume":"18","author":"Dong","year":"2013","journal-title":"Cell Metab."},{"key":"10.1016\/j.isci.2026.117420_bib31","doi-asserted-by":"crossref","DOI":"10.1002\/hsr2.70034","article-title":"Exercise-Induced cytokines, diet, and inflammation and their role in adipose tissue metabolism","volume":"7","author":"Al-Ibraheem","year":"2024","journal-title":"Health Sci. Rep."},{"key":"10.1016\/j.isci.2026.117420_bib32","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1101\/gad.177857.111","article-title":"FGF21 regulates PGC-1\u03b1 and browning of white adipose tissues in adaptive thermogenesis","volume":"26","author":"Fisher","year":"2012","journal-title":"Genes Dev."},{"key":"10.1016\/j.isci.2026.117420_bib33","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.cell.2014.03.065","article-title":"Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis","volume":"157","author":"Rao","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.isci.2026.117420_bib34","doi-asserted-by":"crossref","first-page":"11523","DOI":"10.3390\/ijms231911523","article-title":"The Potential Roles of Myokines in Adipose Tissue Metabolism with Exercise and Cold Exposure","volume":"23","author":"Jiang","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.117420_bib35","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41556-021-00642-9","article-title":"AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1","volume":"23","author":"Shi","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.isci.2026.117420_bib36","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2205626119","article-title":"Loss of adipose TET proteins enhances \u03b2-adrenergic responses and protects against obesity by epigenetic regulation of \u03b23-AR expression","volume":"119","author":"Byun","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117420_bib37","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1111\/bph.14631","article-title":"Adrenoceptors in white, brown, and brite adipocytes","volume":"176","author":"Evans","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.isci.2026.117420_bib38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/21623945.2016.1145846","article-title":"Adrenergic regulation of cellular plasticity in brown, beige\/brite and white adipose tissues","volume":"5","author":"Ramseyer","year":"2016","journal-title":"Adipocyte"},{"key":"10.1016\/j.isci.2026.117420_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2021.101220","article-title":"Macrophage beta2-adrenergic receptor is dispensable for the adipose tissue inflammation and function","volume":"48","author":"Petkevicius","year":"2021","journal-title":"Mol. Metab."},{"key":"10.1016\/j.isci.2026.117420_bib40","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.cmet.2020.07.005","article-title":"Human Brown Adipocyte Thermogenesis Is Driven by \u03b22-AR Stimulation","volume":"32","author":"Blondin","year":"2020","journal-title":"Cell Metab."},{"key":"10.1016\/j.isci.2026.117420_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2024.108927","article-title":"Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis","volume":"27","author":"Dewal","year":"2024","journal-title":"iScience"},{"key":"10.1016\/j.isci.2026.117420_bib42","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/cr.2013.64","article-title":"Brown adipose tissue transplantation improves whole-body energy metabolism","volume":"23","author":"Liu","year":"2013","journal-title":"Cell Res."},{"key":"10.1016\/j.isci.2026.117420_bib43","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.mam.2019.06.004","article-title":"The beneficial effects of brown adipose tissue transplantation","volume":"68","author":"White","year":"2019","journal-title":"Mol. Aspects Med."},{"key":"10.1016\/j.isci.2026.117420_bib44","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41467-021-27540-w","article-title":"Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells","volume":"13","author":"Meister","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117420_bib45","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.yjmcc.2010.02.005","article-title":"Beneficial effects of exercise training after myocardial infarction require full eNOS expression","volume":"48","author":"de Waard","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.isci.2026.117420_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2025.123731","article-title":"Mechanisms of aerobic exercise on doxorubicin-induced cardiomyocyte apoptosis: based on AMPK\/PI3K\/AKT signalling pathway","volume":"376","author":"Zhao","year":"2025","journal-title":"Life Sci."},{"key":"10.1016\/j.isci.2026.117420_bib47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.expneurol.2009.10.008","article-title":"Chronic treatment with agonists of beta(2)-adrenergic receptors in neuropathic pain","volume":"221","author":"Yalcin","year":"2010","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.isci.2026.117420_bib48","doi-asserted-by":"crossref","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): a comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226027987?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226027987?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:04:08Z","timestamp":1791594248000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004226027987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":48,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S2589004226027987"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2026.117420","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exercise-induced adipose tissue ADRB2-PGC1\u03b1-FGF21 signaling protects against pathological cardiac hypertrophy","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2026.117420","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117420"}}