{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:56:56Z","timestamp":1782233816571,"version":"3.54.5"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005667","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa e Inova\u00e7\u00e3o do Estado de Santa Catarina","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study investigates the role of Hepatocyte Nuclear Factor 4\u03b1 (HNF4\u03b1) in the adaptation of pancreatic \u03b2-cells to an HFD-induced obesogenic environment, focusing on \u03b2 cell mass expansion and metabolic adaptations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main methods<\/jats:title><jats:p>We utilized an HNF4\u03b1 knockout (KO) mouse model, with CRE-recombinase enzyme activation confirmed through tamoxifen administration. KO and Control (CTL) mice were fed an HFD for 20 weeks. We monitored body weight, food intake, glucose tolerance, insulin sensitivity, and insulinemia. Also, to assess structural and metabolic changes, histological analyses of pancreatic islets and liver tissue were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key findings<\/jats:title><jats:p>KO mice displayed lower fasting blood glucose levels compared to CTL mice after tamoxifen administration, indicating impaired glucose-regulated insulin secretion. HFD-fed KO mice consumed less food but exhibited greater weight gain and perigonadal fat accumulation, reflecting higher energy efficiency. Histological analysis revealed more pronounced liver steatosis and fibrosis in KO mice on HFD. Glucose intolerance and insulin resistance were exacerbated in KO mice, highlighting their inability to adapt to increased metabolic demand. Structural analysis showed that KO mice failed to exhibit HFD-induced \u03b2 cell mass expansion, resulting in reduced islet diameter and number, confirming the critical role of HNF4\u03b1 in \u03b2 cell adaptation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study demonstrates that HNF4\u03b1 is essential for the proper metabolic and structural adaptation of pancreatic \u03b2-cells in response to an obesogenic environment. The lack of HNF4\u03b1 impairs \u03b2 cell functionality, leading to increased susceptibility to glucose intolerance and insulin resistance. These findings underscore the importance of HNF4\u03b1 in maintaining glucose homeostasis and highlight its potential as a therapeutic target for diabetes management in obesity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1511813","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T05:10:55Z","timestamp":1734412255000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Hepatocyte nuclear factor 4-\u03b1 is necessary for high fat diet-induced pancreatic \u03b2-cell mass expansion and metabolic compensations"],"prefix":"10.3389","volume":"15","author":[{"given":"Francieli Caroline","family":"de Ramos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robson","family":"Barth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos 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