{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:00:30Z","timestamp":1778774430191,"version":"3.51.4"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008749","name":"American College of Sports Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008749","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Fibroblast growth factor 21 (FGF21) is a metabolic regulator that may increase in circulation following exercise. This study was undertaken to determine if changes to FGF21 post-exercise are dependent on biological sex and exercise modality. Secondary analyses were conducted to determine if the post-exercise rise in FGF21 was associated with upstream signaling factors (glucagon, epinephrine, glucose) and excess post-exercise oxygen consumption (EPOC) response. Following a randomized crossover design, male and female participants completed two, thirty minute exercise protocols \u2013 during the steady state (SS) protocol, participants cycled at 70% of VO<jats:sub>2peak<\/jats:sub> and during the sprint interval exercise (IE) protocol participants completed six, thirty second \u201call out\u201d sprints against 7.5% of body weight with four and half minutes of active recovery between sprints. Blood samples were taken at baseline, immediately post-exercise (IPE), and 1-hour post-exercise. Oxygen consumption was monitored continuously throughout the trials. In males, FGF21 levels were increased at 1-hour post-exercise with no difference between conditions; in females, FGF21 levels were unchanged as a result of exercise. Comparison of the post-exercise FGF21 incremental area under the curve revealed that in the SS condition males had a greater FGF21 response than females and that within males the SS condition had a greater response than the IE condition. Exercise significantly increased FGF21 levels in males, but not in females. In males, FGF21 levels were greater in the SS condition than in the IE condition.<\/jats:p>","DOI":"10.1371\/journal.pone.0321738","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T20:03:03Z","timestamp":1748548983000},"page":"e0321738","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of exercise on Fibroblast Growth Factor 21 levels in healthy males and females"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6130-0152","authenticated-orcid":true,"given":"Matthew","family":"Peterson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen A.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LesLee","family":"Funderburk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"issue":"6","key":"pone.0321738.ref001","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1172\/JCI23606","article-title":"FGF-21 as a novel metabolic regulator","volume":"115","author":"A Kharitonenkov","year":"2005","journal-title":"J Clin Invest"},{"issue":"3","key":"pone.0321738.ref002","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cmet.2013.08.005","article-title":"The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes","volume":"18","author":"G Gaich","year":"2013","journal-title":"Cell Metab"},{"issue":"9","key":"pone.0321738.ref003","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/nm.3250","article-title":"FGF21 contributes to neuroendocrine control of female reproduction","volume":"19","author":"BM Owen","year":"2013","journal-title":"Nat Med"},{"issue":"12","key":"pone.0321738.ref004","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.2337\/db09-0713","article-title":"Fibroblast growth factor-21 is induced in human skeletal muscles by hyperinsulinemia","volume":"58","author":"P Hojman","year":"2009","journal-title":"Diabetes"},{"issue":"5","key":"pone.0321738.ref005","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/osp4.360","article-title":"Increased fructose consumption has sex\u2010specific effects on fibroblast growth factor 21 levels in humans","volume":"5","author":"M Rodgers","year":"2019","journal-title":"Obesity Science & Practice"},{"issue":"2","key":"pone.0321738.ref006","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.cmet.2008.06.014","article-title":"The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man","volume":"8","author":"C G\u00e4lman","year":"2008","journal-title":"Cell Metab"},{"issue":"5","key":"pone.0321738.ref007","article-title":"Acute exercise induces FGF21 expression in mice and in healthy humans","volume":"8","author":"KH Kim","year":"2013","journal-title":"PLoS One"},{"issue":"15","key":"pone.0321738.ref008","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.122737","article-title":"Divergent effects of resistance and endurance exercise on plasma bile acids, FGF19, and FGF21 in humans","volume":"3","author":"T Morville","year":"2018","journal-title":"JCI Insight"},{"issue":"8","key":"pone.0321738.ref009","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.molmet.2015.06.001","article-title":"Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans","volume":"4","author":"JS Hansen","year":"2015","journal-title":"Mol Metab"},{"issue":"12","key":"pone.0321738.ref010","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.12828","article-title":"Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation","volume":"4","author":"Y Tanimura","year":"2016","journal-title":"Physiol Rep"},{"issue":"10","key":"pone.0321738.ref011","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1139\/apnm-2018-0818","article-title":"Effect of exercise intensity on circulating hepatokine concentrations in healthy men","volume":"44","author":"SA Willis","year":"2019","journal-title":"Appl Physiol Nutr Metab"},{"issue":"1","key":"pone.0321738.ref012","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jesf.2023.11.002","article-title":"Acute effect of exercise intensity on circulating FGF-21, FSTL-1, cathepsin B, and BDNF in young men","volume":"22","author":"M Ji","year":"2024","journal-title":"J Exerc Sci Fit"},{"key":"pone.0321738.ref013","doi-asserted-by":"crossref","first-page":"155137","DOI":"10.1016\/j.metabol.2022.155137","article-title":"Effects of aerobic exercise on fibroblast growth factor 21 in overweight and obesity. A systematic review","volume":"129","author":"M Porflitt-Rodr\u00edguez","year":"2022","journal-title":"Metabolism"},{"issue":"1","key":"pone.0321738.ref014","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s42000-020-00245-3","article-title":"Impact of acute exercise on immediate and following early post-exercise FGF-21 concentration in adults: systematic review and meta-analysis","volume":"20","author":"M Khalafi","year":"2021","journal-title":"Hormones (Athens)"},{"issue":"3","key":"pone.0321738.ref015","first-page":"209","article-title":"Higher insulin-sensitizing response after sprint interval compared to continuous exercise","volume":"36","author":"JF Ortega","year":"2015","journal-title":"Int J Sports Med"},{"issue":"5","key":"pone.0321738.ref016","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s00421-012-2535-1","article-title":"Appetite, gut hormone and energy intake responses to low volume sprint interval and traditional endurance exercise","volume":"113","author":"K Deighton","year":"2013","journal-title":"Eur J Appl Physiol"},{"issue":"8","key":"pone.0321738.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0022976","article-title":"Paradoxical regulation of human FGF21 by both fasting and feeding signals: is FGF21 a nutritional adaptation factor?","volume":"6","author":"T Uebanso","year":"2011","journal-title":"PLoS One"},{"issue":"6","key":"pone.0321738.ref018","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1152\/japplphysiol.01431.2005","article-title":"Glucose kinetics differ between women and men, during and after exercise","volume":"100","author":"TJ Horton","year":"2006","journal-title":"J Appl Physiol (1985)"},{"issue":"6","key":"pone.0321738.ref019","doi-asserted-by":"crossref","DOI":"10.1152\/ajpendo.2001.280.6.E898","article-title":"Substrate utilization during endurance exercise in men and women after endurance training","volume":"280","author":"SL Carter","year":"2001","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"pone.0321738.ref020","volume-title":"ACSM\u2019s Guidelines for Exercise Testing and Prescription","year":"2018"},{"issue":"5","key":"pone.0321738.ref021","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0038022","article-title":"Exercise increases serum fibroblast growth factor 21 (FGF21) levels","volume":"7","author":"D Cuevas-Ramos","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"pone.0321738.ref022","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/cen.13162","article-title":"Acute endurance exercise lowers serum fibroblast growth factor 21 levels in Japanese men","volume":"85","author":"H Taniguchi","year":"2016","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"9","key":"pone.0321738.ref023","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.numecd.2015.06.002","article-title":"Attenuated fibroblast growth factor 21 response to acute aerobic exercise in obese individuals","volume":"25","author":"AL Slusher","year":"2015","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"pone.0321738.ref024","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.3389\/fphys.2019.01188","article-title":"Examination of the Myokine Response in Pregnant and Non-pregnant Women Following an Acute Bout of Moderate-Intensity Walking","volume":"10","author":"KA Hutchinson","year":"2019","journal-title":"Front Physiol"},{"issue":"8","key":"pone.0321738.ref025","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.molmet.2016.05.010","article-title":"Fibroblast growth factor 21 has no direct role in regulating fertility in female mice","volume":"5","author":"G Singhal","year":"2016","journal-title":"Mol Metab"},{"issue":"4","key":"pone.0321738.ref026","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1113\/EP088351","article-title":"Age-related bone loss is associated with FGF21 but not IGFBP1 in healthy adults","volume":"105","author":"SY Lee","year":"2020","journal-title":"Exp Physiol"},{"issue":"2","key":"pone.0321738.ref027","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1007\/s12020-017-1507-y","article-title":"Association between fibroblast growth factor 21 and bone mineral density in adults","volume":"59","author":"R-H Hao","year":"2018","journal-title":"Endocrine"},{"key":"pone.0321738.ref028","doi-asserted-by":"crossref","DOI":"10.1101\/2025.02.16.638516","article-title":"Relationship Between Circulating FGF21 and Bone Mineral Density: An Exploratory Study","author":"M Peterson","year":"2025"},{"issue":"3","key":"pone.0321738.ref029","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/ATVBAHA.111.242461","article-title":"Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women","volume":"32","author":"L Persson","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"5","key":"pone.0321738.ref030","doi-asserted-by":"crossref","DOI":"10.1152\/ajpendo.00330.2013","article-title":"Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the induction of FGF21 as a myokine","volume":"306","author":"S Keipert","year":"2014","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"27","key":"pone.0321738.ref031","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1016\/j.febslet.2008.10.021","article-title":"FGF21 is an Akt-regulated myokine","volume":"582","author":"Y Izumiya","year":"2008","journal-title":"FEBS Lett"},{"issue":"2","key":"pone.0321738.ref032","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/jmcb\/mjw013","article-title":"The FGF21-adiponectin axis in controlling energy and vascular homeostasis","volume":"8","author":"X Hui","year":"2016","journal-title":"J Mol Cell Biol"},{"key":"pone.0321738.ref033","article-title":"Evaluation of the Size, Shape, and Consistency of the Liver","volume-title":"Clinical Methods: The History, Physical, and Laboratory Examinations","author":"DC. Wolf","year":"1990"},{"issue":"6","key":"pone.0321738.ref034","article-title":"Regulators of human white adipose browning: evidence for sympathetic control and sexual dimorphic responses to sprint interval training","volume":"9","author":"RL Scalzo","year":"2014","journal-title":"PLoS One"},{"key":"pone.0321738.ref035","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.3389\/fphys.2018.01735","article-title":"Myokine Response to High-Intensity Interval vs. Resistance Exercise: An Individual Approach","volume":"9","author":"Z He","year":"2018","journal-title":"Front Physiol"},{"issue":"14","key":"pone.0321738.ref036","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.2165\/00007256-200333140-00002","article-title":"Effect of exercise intensity, duration and mode on post-exercise oxygen consumption","volume":"33","author":"E B\u00f8rsheim","year":"2003","journal-title":"Sports Med"},{"issue":"6","key":"pone.0321738.ref037","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1152\/jappl.1990.68.6.2362","article-title":"Effect of exercise intensity and duration on postexercise metabolism","volume":"68","author":"CJ Gore","year":"1990","journal-title":"J Appl Physiol (1985)"},{"issue":"2","key":"pone.0321738.ref038","doi-asserted-by":"crossref","first-page":"45","DOI":"10.20463\/jenb.2019.0016","article-title":"Effect of interval exercise versus continuous exercise on excess post-exercise oxygen consumption during energy-homogenized exercise on a cycle ergometer","volume":"23","author":"W-S Jung","year":"2019","journal-title":"J Exerc Nutrition Biochem"},{"issue":"3","key":"pone.0321738.ref039","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.cmet.2012.08.002","article-title":"\u03b2Klotho is required for fibroblast growth factor 21 effects on growth and metabolism","volume":"16","author":"X Ding","year":"2012","journal-title":"Cell Metab"},{"issue":"12","key":"pone.0321738.ref040","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.1210\/en.2008-0816","article-title":"Fibroblast growth factor 21 corrects obesity in mice","volume":"149","author":"T Coskun","year":"2008","journal-title":"Endocrinology"},{"key":"pone.0321738.ref041","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.fob.2013.12.001","article-title":"Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs","volume":"4","author":"FM Keane","year":"2013","journal-title":"FEBS Open Bio"},{"issue":"5","key":"pone.0321738.ref042","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1042\/BJ20151085","article-title":"Circulating FGF21 proteolytic processing mediated by fibroblast activation protein","volume":"473","author":"EY Zhen","year":"2016","journal-title":"Biochem J"},{"issue":"12","key":"pone.0321738.ref043","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1249\/MSS.0000000000002073","article-title":"Methodological Recommendations for Menstrual Cycle Research in Sports and Exercise","volume":"51","author":"X Janse DE Jonge","year":"2019","journal-title":"Med Sci Sports Exerc"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0321738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T20:03:19Z","timestamp":1748548999000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0321738"}},"subtitle":[],"editor":[{"given":"Matias A.","family":"Avila","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0321738","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,29]]}}}