{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:18:22Z","timestamp":1788153502144,"version":"build-2803163510"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK121215, DK139539"],"award-info":[{"award-number":["DK121215, DK139539"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The rising prevalence of metabolic disorders highlights the need to identify targetable pathways. Although hypothalamic AgRP neuron signaling influences energy balance, the beneficial role of fibroblast growth factor receptor 1 (FGFR1) within these neurons remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed an AAV-mediated CRISPR\/Cas9 activation system to achieve AgRP neuron-specific overexpression of FGFR1 in adult mice. Metabolic phenotypes were assessed during high-fat diet (HFD) feeding, and mechanistic insights were gained using GT1\u20137 hypothalamic cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>FGFR1 overexpression in AgRP neurons attenuated high-fat diet (HFD)-induced weight gain and improved glucose tolerance, effects that were associated with reduced energy intake. Mechanistically, FGFR1 overexpression correlated with increased FOXO1 phosphorylation and reduced AgRP mRNA expression, suggesting a potential FGFR1-FOXO1 regulatory axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify a contributory role for AgRP neuronal FGFR1 signaling in modulating metabolic outcomes under HFD conditions and suggest that this pathway may represent a potential avenue for further investigation in the context of obesity and diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1905737","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:28:12Z","timestamp":1788150492000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Overexpression of FGFR1 in AgRP neurons protects against obesity and improves glucose homeostasis"],"prefix":"10.3389","volume":"17","author":[{"given":"Daniel","family":"Shookster","sequence":"first","affiliation":[{"name":"East Carolina Diabetes and Obesity Institute, East Carolina University","place":["Greenville, NC, United States"]},{"name":"Department of Kinesiology, East Carolina University","place":["Greenville, NC, United States"]},{"name":"Human Performance Laboratory, College of Human Performance and Health, East Carolina University","place":["Greenville, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahjanelle","family":"Martin","sequence":"additional","affiliation":[{"name":"East Carolina Diabetes and Obesity Institute, East Carolina University","place":["Greenville, NC, United States"]},{"name":"Department of Kinesiology, East Carolina University","place":["Greenville, NC, United States"]},{"name":"Human Performance Laboratory, College of Human Performance and Health, East Carolina University","place":["Greenville, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Gunn","sequence":"additional","affiliation":[{"name":"East Carolina Diabetes and Obesity Institute, East Carolina University","place":["Greenville, NC, United States"]},{"name":"Department of Kinesiology, East Carolina University","place":["Greenville, NC, United States"]},{"name":"Human Performance Laboratory, College of Human Performance and Health, East Carolina University","place":["Greenville, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shea","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"East Carolina Diabetes and Obesity Institute, East Carolina University","place":["Greenville, NC, United States"]},{"name":"Department of Kinesiology, East Carolina University","place":["Greenville, NC, United States"]},{"name":"Human Performance Laboratory, College of Human Performance and 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