{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:35:36Z","timestamp":1785285336605,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chronic Non-Communicable Diseases-National Science and Technology Major Project of China","award":["2404ZD0531300"],"award-info":[{"award-number":["2404ZD0531300"]}]},{"name":"Chronic Non-Communicable Diseases-National Science and Technology Major Project of China","award":["32230047"],"award-info":[{"award-number":["32230047"]}]},{"name":"Chronic Non-Communicable Diseases-National Science and Technology Major Project of China","award":["2023YFA1801100"],"award-info":[{"award-number":["2023YFA1801100"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2404ZD0531300"],"award-info":[{"award-number":["2404ZD0531300"]}],"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":["32230047"],"award-info":[{"award-number":["32230047"]}],"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":["2023YFA1801100"],"award-info":[{"award-number":["2023YFA1801100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China","award":["2404ZD0531300"],"award-info":[{"award-number":["2404ZD0531300"]}]},{"name":"National Key Research and Development Program of China","award":["32230047"],"award-info":[{"award-number":["32230047"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFA1801100"],"award-info":[{"award-number":["2023YFA1801100"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2404ZD0531300"],"award-info":[{"award-number":["2404ZD0531300"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["32230047"],"award-info":[{"award-number":["32230047"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2023YFA1801100"],"award-info":[{"award-number":["2023YFA1801100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Fibroblast growth factor 21 (FGF21), a secreted protein, plays a crucial role in regulating metabolism and energy homeostasis. Nevertheless, the expression pattern of Fgf21 across diverse tissues and its responsiveness to various dietary regimens remain incompletely understood. Methods: In this study, we developed a Fgf21-enhanced green fluorescent protein (EGFP) reporter mouse model to explore the expression of endogenous Fgf21 in different tissues under four dietary conditions: normal chow, low-protein diet, fasting, and fasting-refeeding. Results: A low-protein diet was found to induce Fgf21 expression in both the liver and skeletal muscle. Notably, Fgf21 was predominantly expressed in the periportal region of the liver. In the pancreas, Fgf21 exhibited a patchy expression pattern in the exocrine portion, but was absent in the endocrine part, regardless of the dietary regimens. Regarding the spleen, fasting triggered the expression of Fgf21, which was mainly localized in the red pulp area. Moreover, under fasting conditions, Fgf21 showed a scattered expression pattern in the small intestine. Conclusions: The Fgf21-EGFP reporter mouse model serves as a valuable tool for dissecting the expression of endogenous Fgf21 in different tissues under various dietary and stress conditions. Further investigations using this model may contribute to uncovering the hitherto unrecognized functions of locally produced FGF21.<\/jats:p>","DOI":"10.3390\/nu17071179","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T06:06:35Z","timestamp":1743141995000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Distinct Fgf21 Expression Patterns in Various Tissues in Response to Different Dietary Regimens Using a Reporter Mouse Model"],"prefix":"10.3390","volume":"17","author":[{"given":"Xinhui","family":"Zhang","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6630-0693","authenticated-orcid":false,"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0167-4781(00)00067-1","article-title":"Identification of a novel FGF, FGF-21, preferentially expressed in the liver","volume":"1492","author":"Nishimura","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.molmet.2013.12.003","article-title":"Inventing new medicines: The FGF21 story","volume":"3","author":"Kharitonenkov","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-nutr-071816-064800","article-title":"Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis","volume":"38","author":"BonDurant","year":"2018","journal-title":"Annu. Rev. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s42255-021-00354-2","article-title":"Metabolic Messengers: FGF21","volume":"3","author":"Flippo","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.tem.2024.02.001","article-title":"Current status and future perspectives of FGF21 analogues in clinical trials","volume":"35","author":"Chui","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.1073\/pnas.0701600104","article-title":"BetaKlotho is required for metabolic activity of fibroblast growth factor 21","volume":"104","author":"Ogawa","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E1105","DOI":"10.1152\/ajpendo.00348.2009","article-title":"Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models--association with liver and adipose tissue effects","volume":"297","author":"Xu","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.cmet.2017.09.005","article-title":"FGF19, FGF21, and an FGFR1\/beta-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia","volume":"26","author":"Lan","year":"2017","journal-title":"Cell Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chen, G., Chen, L., Li, X., and Mohammadi, M. (Nat. Rev. Drug Discov., 2025). FGF-based drug discovery: Advances and challenges, Nat. Rev. Drug Discov., online ahead of print.","DOI":"10.1038\/s41573-024-01125-w"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cmet.2016.09.001","article-title":"Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework","volume":"24","author":"Cogger","year":"2016","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.cmet.2007.05.003","article-title":"Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21","volume":"5","author":"Inagaki","year":"2007","journal-title":"Cell Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.cmet.2007.05.002","article-title":"Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states","volume":"5","author":"Badman","year":"2007","journal-title":"Cell Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cmet.2015.12.003","article-title":"FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver","volume":"23","author":"BonDurant","year":"2016","journal-title":"Cell Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1172\/JCI85946","article-title":"A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution","volume":"126","author":"Maida","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_15","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":"Galman","year":"2008","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4601","DOI":"10.1172\/JCI83349","article-title":"FGF21 and the late adaptive response to starvation in humans","volume":"125","author":"Fazeli","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1172\/JCI74915","article-title":"FGF21 is an endocrine signal of protein restriction","volume":"124","author":"Laeger","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.molmet.2014.09.008","article-title":"Fructose ingestion acutely stimulates circulating FGF21 levels in humans","volume":"4","author":"Dushay","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.molmet.2016.11.001","article-title":"Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates","volume":"6","author":"Lundsgaard","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/j.molmet.2017.08.004","article-title":"Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury","volume":"6","author":"Desai","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.molmet.2018.03.010","article-title":"FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest","volume":"11","author":"Soberg","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cmet.2015.12.008","article-title":"FGF21 Regulates Sweet and Alcohol Preference","volume":"23","author":"Talukdar","year":"2016","journal-title":"Cell Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.2337\/db14-0595","article-title":"Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding","volume":"63","author":"Markan","year":"2014","journal-title":"Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1210\/me.2010-0142","article-title":"Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse","volume":"24","author":"Bookout","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cmet.2016.12.004","article-title":"FGF21 Is an Exocrine Pancreas Secretagogue","volume":"25","author":"Coate","year":"2017","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1053\/j.gastro.2009.07.064","article-title":"Fibroblast growth factor 21 reduces the severity of cerulein-induced pancreatitis in mice","volume":"137","author":"Johnson","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1042\/BCJ20200220","article-title":"The autocrine role of FGF21 in cultured adipocytes","volume":"477","author":"Justesen","year":"2020","journal-title":"Biochem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.cmet.2017.08.003","article-title":"The FGF21-CCL11 Axis Mediates Beiging of White Adipose Tissues by Coupling Sympathetic Nervous System to Type 2 Immunity","volume":"26","author":"Huang","year":"2017","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E469","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":"Keipert","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nm.3014","article-title":"Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine","volume":"19","author":"Kim","year":"2013","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.celrep.2016.04.057","article-title":"Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle","volume":"15","author":"Vandanmagsar","year":"2016","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.bbrc.2022.06.045","article-title":"Bicistronic reporter mice for monitoring of Fgf21 expression","volume":"619","author":"Pham","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1126\/science.abi9547","article-title":"Zonated leucine sensing by Sestrin-mTORC1 in the liver controls the response to dietary leucine","volume":"377","author":"Cangelosi","year":"2022","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.biopha.2018.10.198","article-title":"Fibroblast growth factor 21 improves glucose homeostasis partially via down-regulation of Na(+)-d-glucose cotransporter SGLT1 in the small intestine","volume":"109","author":"Wang","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.tem.2014.07.002","article-title":"Protein and amino acid restriction, aging and disease: From yeast to humans","volume":"25","author":"Mirzaei","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1038\/s41467-022-29499-8","article-title":"FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice","volume":"13","author":"Hill","year":"2022","journal-title":"Nat. Commun."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:04:13Z","timestamp":1760029453000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":36,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["nu17071179"],"URL":"https:\/\/doi.org\/10.3390\/nu17071179","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]}}}