{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:30:58Z","timestamp":1789605058899,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["15SDG25710438"],"award-info":[{"award-number":["15SDG25710438"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["25POST1377539"],"award-info":[{"award-number":["25POST1377539"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["25PRE1361334"],"award-info":[{"award-number":["25PRE1361334"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["NIH DK125405"],"award-info":[{"award-number":["NIH DK125405"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["T32DK112751\u201001"],"award-info":[{"award-number":["T32DK112751\u201001"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n Our previous studies showed that mice lacking the mitochondrial fusion protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) have high metabolic rates and are resistant to diet\u2010induced obesity (DIO) via effects partially mediated by independent actions of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) secretion from BAT. We examined whether FGF21 and GDF15 act synergistically, contributing to the systemic metabolic adaptations reported in OPA1 BKO mice.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We generated mice simultaneously lacking the\n Opa1<\/jats:italic>\n ,\n Fgf21<\/jats:italic>\n , and\n Gdf15<\/jats:italic>\n genes in thermogenic adipocytes (TKO) and assessed energy homeostasis and glucose metabolism after regular chow or high\u2010fat diet feeding.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Young TKO mice fed regular chow had impaired glucose tolerance, while insulin sensitivity was unchanged. Notably, combined\n Fgf21<\/jats:italic>\n and\n Gdf15<\/jats:italic>\n deletion in OPA1 BKO significantly blunted the resistance to DIO and insulin resistance observed in OPA1 BKO mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n FGF21 and GDF15 act synergistically to maintain glucose homeostasis and promote resistance to DIO in mice lacking OPA1 in BAT, highlighting the potential of combined therapies using FGF21 and GDF15 for the treatment of metabolic disorders.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/oby.70004","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T01:50:47Z","timestamp":1756864247000},"page":"1909-1920","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["FGF21<\/scp>\n and\n GDF15<\/scp>\n Act Synergistically to Regulate Systemic Metabolic Homeostasis in Mice Lacking\n OPA1<\/scp>\n in\u00a0Thermogenic Adipocytes"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9441-9077","authenticated-orcid":false,"given":"Joshua","family":"Peterson","sequence":"first","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashree","family":"Jena","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-9929","authenticated-orcid":false,"given":"Ayushi","family":"Sood","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly","family":"Roitershtein","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Smith","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata O.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City Iowa 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