{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:04:05Z","timestamp":1789416245659,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005916","name":"Universidad de La Frontera","doi-asserted-by":"publisher","award":["DIUFRO DI22-0063"],"award-info":[{"award-number":["DIUFRO DI22-0063"]}],"id":[{"id":"10.13039\/501100005916","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Early-life stress and dietary habits are key determinants of metabolic health. This study investigates the combined effects of maternal separation (MS) and a post-weaning high-fat diet (HFD) on liver morphology in male C57BL\/6 mice. Methods: Male mice were subjected to MS during early postnatal life or kept unmanipulated (UM). After weaning, animals were assigned to either a control diet (CD) or an HFD, forming four groups: UM-CD, UM-HFD, MS-CD, and MS-HFD. Liver histology, collagen deposition, and both morphometric and stereological parameters were assessed following 16 weeks of dietary intervention. Results: MS and HFD independently altered liver structure, while the combination of both factors intensified these changes. The MS-HFD group exhibited pronounced steatosis, mixed inflammatory infiltrates, and hepatocellular ballooning, with a significantly higher NAFLD Activity Score (NAS). No significant differences were observed in liver fibrosis. Morphometric analysis revealed increased body mass in HFD-fed groups and elevated liver mass in MS-HFD. Liver volume was higher in MS-HFD, though not significantly. Liver stereology revealed reduced numerical density of hepatocytes (Nvhep) and increased surface density (Svhep) in MS groups, with the most pronounced effects in MS-HFD. Conclusions: Maternal separation amplifies the hepatic alterations induced by HFD, promoting early inflammatory and steatotic changes. These findings highlight the significance of early-life stress as a factor increasing susceptibility to diet-induced liver damage.<\/jats:p>","DOI":"10.3390\/nu17101619","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T04:13:44Z","timestamp":1746764024000},"page":"1619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["When Timing Matters: Effects of Maternal Separation and Post-Weaning High-Fat Diet on Liver Morphology in a Rodent Model"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3686-6757","authenticated-orcid":false,"given":"Mariano","family":"del Sol","sequence":"first","affiliation":[{"name":"Center of Excellence in Morphological and Surgical Studies, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javiera","family":"Navarrete","sequence":"additional","affiliation":[{"name":"Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Garc\u00eda-Orozco","sequence":"additional","affiliation":[{"name":"Center of Excellence in Morphological and Surgical Studies, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5949-4407","authenticated-orcid":false,"given":"Jhonatan","family":"Duque-Colorado","sequence":"additional","affiliation":[{"name":"Center of Excellence in Morphological and Surgical Studies, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4207-8928","authenticated-orcid":false,"given":"Zaida","family":"S\u00f3cola-Barsallo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universidad T\u00e9cnica Particular de Loja, San Cayetano Alto, Calle Par\u00eds, Loja 110107, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3184-6482","authenticated-orcid":false,"given":"Cristian","family":"Sandoval","sequence":"additional","affiliation":[{"name":"Escuela de Tecnolog\u00eda M\u00e9dica, Facultad de Salud, Universidad Santo Tom\u00e1s, Los Carreras 753, Osorno 5310431, Chile"},{"name":"Departamento de Medicina Interna, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4106-3548","authenticated-orcid":false,"given":"B\u00e9lgica","family":"V\u00e1squez","sequence":"additional","affiliation":[{"name":"Center of Excellence in Morphological and Surgical Studies, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"},{"name":"Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Avenida Francisco Salazar 01145, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1365-2796.2007.01809.x","article-title":"The origins of the developmental origins theory","volume":"261","author":"Barker","year":"2007","journal-title":"J. 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