{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:38:19Z","timestamp":1784403499951,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa Institucional de Obesidad y Diabetes, Instituto de Investigaciones Biom\u00e9dicas, UNAM","award":["9028"],"award-info":[{"award-number":["9028"]}]},{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencias, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["748035"],"award-info":[{"award-number":["748035"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Gestational exposure to a high-fat diet (HFD) reprograms hypothalamic orexigenic circuits prenatally. However, whether astrocytes, critical modulators of this system, are also imprinted by HFD in the fetal brain remains unknown. We investigated the impact of HFD on the prenatal neuroglial architecture of the lateral hypothalamic area (LHA). Methods: Female Wistar rats were fed a control or a 60% fat diet for 12 weeks. Upon reaching obesity (Lee index \u2265 310), dams were mated. Fetuses were harvested via cesarean section at term, and their brains were processed for immunohistochemistry and morphometry to assess cell proliferation, orexin neuron density, and astrocytic reactivity in the LHA. Results: HFD significantly increased cell proliferation and orexinergic neuron density, and induced early signs of astrocyte reactivity in the fetal LHA. These findings reveal that both neuronal and glial components of the LHA orexigenic axis are structurally reprogrammed before birth. Conclusions: This study provides the first evidence that HFD simultaneously alters neuronal and glial developmental trajectories in the fetal hypothalamus. The concurrent programming of astrocytes and orexigenic neurons suggests a prenatal origin for neuroinflammatory susceptibility, reframing obesity as a neurodevelopmental disorder shaped by early life nutritional environments.<\/jats:p>","DOI":"10.3390\/brainsci16010052","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:34:23Z","timestamp":1767198863000},"page":"52","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gestational High-Fat Diet Drives Premature Differentiation of Orexigenic Neurons and Reactivity of Astrocytes in the Fetal Rat Lateral Hypothalamus"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6034-0125","authenticated-orcid":false,"given":"Nuria","family":"Galindo-Solano","sequence":"first","affiliation":[{"name":"Laboratorio de Biolog\u00eda de Sistemas, Departamento de Biolog\u00eda Celular y Fisiolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"},{"name":"Programa de Doctorado en Ciencias Biom\u00e9dicas, Unidad de Posgrado, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximena","family":"Trejo-Villarreal","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de Sistemas, Departamento de Biolog\u00eda Celular y Fisiolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geovanna","family":"D\u00edaz-Olivares","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de Sistemas, Departamento de Biolog\u00eda Celular y Fisiolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Rea-Palomino","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de Sistemas, Departamento de Biolog\u00eda Celular y Fisiolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayna","family":"Montes-Aguirre","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de Sistemas, Departamento de Biolog\u00eda Celular y Fisiolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maricela","family":"Villagr\u00e1n-Santa-Cruz","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Tisular y Reproductora, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Guti\u00e9rrez-Ospina","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de Sistemas, Departamento de Biolog\u00eda Celular y Fisiolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"},{"name":"Coordinaci\u00f3n de Psicobiolog\u00eda y Neurociencias, Facultad de Psicolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00737-020-01057-5","article-title":"The role of prenatal and perinatal factors in eating disorders: A systematic review","volume":"24","author":"Marzola","year":"2021","journal-title":"Arch. 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