{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:07:48Z","timestamp":1772244468780,"version":"3.50.1"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.lfs.2026.124259","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:25:39Z","timestamp":1770395139000},"page":"124259","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Drug repurposing reveals Fmoc-l-leucine as an adipose thermogenesis activator in cold-exposed mice by targeting PPAR\u03b3\/UCP1"],"prefix":"10.1016","volume":"390","author":[{"given":"Mingjie","family":"Feng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenhui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingqi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenghui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaling","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-0467","authenticated-orcid":false,"given":"Zhe","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.lfs.2026.124259_bb0005","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/bmb\/ldw001","article-title":"Freezing and non-freezing cold weather injuries: a systematic review","volume":"117","author":"Heil","year":"2016","journal-title":"Br. Med. Bull."},{"key":"10.1016\/j.lfs.2026.124259_bb0010","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3390\/ijerph19010501","article-title":"Accidental hypothermia: 2021 update","volume":"19","author":"Paal","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"10.1016\/j.lfs.2026.124259_bb0015","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.emc.2016.12.006","article-title":"Frostbite","volume":"35","author":"Handford","year":"2017","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"10.1016\/j.lfs.2026.124259_bb0020","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1001\/jamadermatol.2018.0734","article-title":"Endurance\u2014frostbite, then and now","volume":"154","author":"Dempsey","year":"2018","journal-title":"JAMA Dermatol."},{"key":"10.1016\/j.lfs.2026.124259_bb0025","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1056\/NEJMra1800868","article-title":"Diagnosis and treatment of frostbite","volume":"386","author":"Sheridan","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.lfs.2026.124259_bb0030","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1093\/brain\/awx215","article-title":"Chronic non-freezing cold injury results in neuropathic pain due to a sensory neuropathy","volume":"140","author":"Vale","year":"2017","journal-title":"Brain"},{"key":"10.1016\/j.lfs.2026.124259_bb0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2022.166385","article-title":"Hypoxia-induced nuclear translocation of \u03b2-catenin in the healing process of frostbite","volume":"1868","author":"Isozaki","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. basis Dis."},{"key":"10.1016\/j.lfs.2026.124259_bb0040","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.lfs.2026.124259_bb0045","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202101905RR","article-title":"Topical application of the pharmacological cold mimetic menthol stimulates brown adipose tissue thermogenesis through a TRPM8, UCP1, and norepinephrine dependent mechanism in mice housed at thermoneutrality","volume":"36","author":"McKie","year":"2022","journal-title":"FASEB J."},{"key":"10.1016\/j.lfs.2026.124259_bb0050","first-page":"741","article-title":"The triaging and treatment of cold-induced injuries","volume":"44","author":"Sachs","year":"2015","journal-title":"Dtsch. Arztebl. Int."},{"key":"10.1016\/j.lfs.2026.124259_bb0055","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/1558944718800731","article-title":"The use of t-PA in the treatment of frostbite: a systematic review","volume":"14","author":"Hutchison","year":"2019","journal-title":"Hand"},{"key":"10.1016\/j.lfs.2026.124259_bb0060","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/procel\/pwae055","article-title":"Skin organoid transplantation promotes tissue repair with scarless in frostbite","volume":"16","author":"Wang","year":"2025","journal-title":"Protein Cell"},{"key":"10.1016\/j.lfs.2026.124259_bb0065","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adp2211","article-title":"Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8","volume":"10","author":"Yin","year":"2024","journal-title":"Sci. Adv."},{"key":"10.1016\/j.lfs.2026.124259_bb0070","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1021\/acscentsci.4c01803","article-title":"The fight against frostbite progresses","volume":"10","author":"Eberle","year":"2024","journal-title":"ACS Cent. Sci."},{"key":"10.1016\/j.lfs.2026.124259_bb0075","first-page":"6","article-title":"Expert consensus on the prevention, diagnosis and treatment of cold injury in China, 2020","volume":"8","author":"Jin","year":"2021","journal-title":"Mil. Med. Res."},{"key":"10.1016\/j.lfs.2026.124259_bb0080","article-title":"Interventions for frostbite injuries","volume":"12","author":"Lorentzen","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.lfs.2026.124259_bb0085","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13049-024-01184-3","article-title":"Prolonged critical avalanche burial for nearly 23 h with severe hypothermia and severe frostbite with good recovery: a case report","volume":"32","author":"Gruber","year":"2024","journal-title":"Scand. J. Trauma Resusc. Emerg. Med."},{"key":"10.1016\/j.lfs.2026.124259_bb0090","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/nm.3361","article-title":"Brown and beige fat: development, function and therapeutic potential","volume":"19","author":"Harms","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.lfs.2026.124259_bb0095","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.cell.2012.05.016","article-title":"Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human","volume":"150","author":"Wu","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.lfs.2026.124259_bb0100","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.cmet.2024.01.001","article-title":"Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB","volume":"36","author":"Rahbani","year":"2024","journal-title":"Cell Metab."},{"key":"10.1016\/j.lfs.2026.124259_bb0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2022.106175","article-title":"Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue","volume":"178","author":"Ma","year":"2022","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.lfs.2026.124259_bb0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2022.106136","article-title":"Matrine counteracts obesity in mice via inducing adipose thermogenesis by activating HSF1\/PGC-1\u03b1 axis","volume":"177","author":"Li","year":"2022","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.lfs.2026.124259_bb0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiomed.2022.105992","article-title":"A computational approach to drug repurposing using graph neural networks","volume":"150","author":"Doshi","year":"2022","journal-title":"Comput. Biol. Med."},{"key":"10.1016\/j.lfs.2026.124259_bb0120","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1093\/bib\/bbaa003","article-title":"Exploration of databases and methods supporting drug repurposing: a comprehensive survey","volume":"22","author":"Tanoli","year":"2021","journal-title":"Brief. Bioinform."},{"key":"10.1016\/j.lfs.2026.124259_bb0125","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.cmet.2021.02.007","article-title":"The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity","volume":"33","author":"Chen","year":"2021","journal-title":"Cell Metab."},{"key":"10.1016\/j.lfs.2026.124259_bb0130","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1093\/bib\/bbz176","article-title":"Biomedical data and computational models for drug repositioning: a comprehensive review","volume":"22","author":"Luo","year":"2021","journal-title":"Brief. Bioinform."},{"key":"10.1016\/j.lfs.2026.124259_bb0135","article-title":"Drug repurposing for cancer therapy","volume":"9","author":"Xia","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.lfs.2026.124259_bb0140","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.apsb.2021.09.006","article-title":"Repurposing non-oncology small-molecule drugs to improve cancer therapy: current situation and future directions","volume":"12","author":"Fu","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.lfs.2026.124259_bb0145","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/s41467-021-21330-0","article-title":"Machine learning identifies candidates for drug repurposing in Alzheimer\u2019s disease","volume":"12","author":"Rodriguez","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.lfs.2026.124259_bb0150","doi-asserted-by":"crossref","DOI":"10.1093\/bib\/bbab161","article-title":"Reconciling multiple connectivity scores for drug repurposing","volume":"22","author":"Samart","year":"2021","journal-title":"Brief. Bioinform."},{"key":"10.1016\/j.lfs.2026.124259_bb0155","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.cell.2022.02.004","article-title":"Local hyperthermia therapy induces browning of white fat and treats obesity","volume":"185","author":"Li","year":"2022","journal-title":"Cell"},{"key":"10.1016\/j.lfs.2026.124259_bb0160","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.2337\/db16-1057","article-title":"Mast cells promote seasonal white adipose beiging in humans","volume":"66","author":"Finlin","year":"2017","journal-title":"Diabetes"},{"key":"10.1016\/j.lfs.2026.124259_bb0165","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41586-022-05030-3","article-title":"Brown-fat-mediated tumour suppression by cold-altered global metabolism","volume":"608","author":"Seki","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.lfs.2026.124259_bb0170","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2020.153457","article-title":"Withaferin A exerts an anti-obesity effect by increasing energy expenditure through thermogenic gene expression in high-fat diet-fed obese mice","volume":"82","author":"Lee","year":"2021","journal-title":"Phytomedicine"},{"key":"10.1016\/j.lfs.2026.124259_bb0175","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2337\/db21-0470","article-title":"Withaferin A promotes white adipose browning and prevents obesity through sympathetic nerve-activated Prdm16-FATP1 Axis","volume":"71","author":"Guo","year":"2022","journal-title":"Diabetes"},{"key":"10.1016\/j.lfs.2026.124259_bb0180","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/s42255-018-0021-8","article-title":"Metabolic adaptation and maladaptation in adipose tissue","volume":"1","author":"Chouchani","year":"2019","journal-title":"Nat. Metab."},{"key":"10.1016\/j.lfs.2026.124259_bb0185","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nrm.2016.96","article-title":"Control of brown and beige fat development","volume":"17","author":"Wang","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.lfs.2026.124259_bb0190","doi-asserted-by":"crossref","first-page":"12480","DOI":"10.1073\/pnas.1310261110","article-title":"Fat cells directly sense temperature to activate thermogenesis","volume":"110","author":"Ye","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.lfs.2026.124259_bb0195","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.cell.2012.06.027","article-title":"Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of PPAR\u03b3","volume":"150","author":"Qiang","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.lfs.2026.124259_bb0200","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.cmet.2012.01.019","article-title":"PPARg agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein","volume":"15","author":"Ohno","year":"2012","journal-title":"Cell Metab."},{"key":"10.1016\/j.lfs.2026.124259_bb0205","doi-asserted-by":"crossref","DOI":"10.1172\/JCI170072","article-title":"A PPAR\u03b3\/long noncoding RNA axis regulates adipose thermoneutral remodeling in mice","volume":"133","author":"Zhang","year":"2023","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.lfs.2026.124259_bb0210","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S1097-2765(01)00353-7","article-title":"A unique PPAR\u03b3 ligand with potent insulin-sensitizing yet weak adipogenic activity","volume":"8","author":"Rocchi","year":"2001","journal-title":"Mol. Cell"},{"key":"10.1016\/j.lfs.2026.124259_bb0215","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1038\/s42255-022-00644-3","article-title":"Cdo1 promotes PPAR\u03b3-mediated adipose tissue lipolysis in male mice","volume":"4","author":"Guo","year":"2022","journal-title":"Nat. Metab."},{"key":"10.1016\/j.lfs.2026.124259_bb0220","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.phrs.2016.02.028","article-title":"PPAR\u03b3 signaling and emerging opportunities for improved therapeutics","volume":"111","author":"Wang","year":"2016","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.lfs.2026.124259_bb0225","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2023.103059","article-title":"Selective PPAR\u03b3 modulator diosmin improves insulin sensitivity and promotes browning of white fat","volume":"299","author":"Yu","year":"2023","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.lfs.2026.124259_bb0230","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.cmet.2012.03.009","article-title":"In vivo identification of bipotential adipocyte progenitors recruited by \u03b23-adrenoceptor activation and high-fat feeding","volume":"15","author":"Lee","year":"2012","journal-title":"Cell Metab."},{"key":"10.1016\/j.lfs.2026.124259_bb0235","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/s41569-021-00569-6","article-title":"PPAR control of metabolism and cardiovascular functions","volume":"18","author":"Montaigne","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.lfs.2026.124259_bb0240","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1016\/j.celrep.2020.02.032","article-title":"Shared PPAR\u03b1\/\u03b3 target genes regulate brown adipocyte thermogenic function","volume":"30","author":"Shen","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.lfs.2026.124259_bb0245","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.cmet.2024.10.018","article-title":"Cold-induced thermogenesis requires neutral-lipase-mediated intracellular lipolysis in brown adipocytes","volume":"37","author":"Mouisel","year":"2024","journal-title":"Cell Metab."},{"key":"10.1016\/j.lfs.2026.124259_bb0250","doi-asserted-by":"crossref","first-page":"E1736","DOI":"10.1152\/ajpendo.00122.2007","article-title":"PPAR\u03b3 regulates adipose triglyceride lipase in adipocytes in vitro and in vivo","volume":"293","author":"Kershaw","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320526000676?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320526000676?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T01:18:41Z","timestamp":1772241521000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0024320526000676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":50,"alternative-id":["S0024320526000676"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2026.124259","relation":{},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Drug repurposing reveals Fmoc-l-leucine as an adipose thermogenesis activator in cold-exposed mice by targeting PPAR\u03b3\/UCP1","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2026.124259","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"124259"}}