{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:27:27Z","timestamp":1787646447920,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["409165\/2024-7 (INCT Call 46\/2024)"],"award-info":[{"award-number":["409165\/2024-7 (INCT Call 46\/2024)"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"award":["409165\/2024-7 (INCT Call 46\/2024)"],"award-info":[{"award-number":["409165\/2024-7 (INCT Call 46\/2024)"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Obesity is a multifactorial disorder with increasing global prevalence, highlighting the importance of identifying early-life factors that may influence long-term metabolic outcomes. While metformin is widely used to improve metabolic dysfunction in adulthood, whether neonatal exposure to this drug modifies adult responses to subsequent dietary challenges remains poorly understood. This exploratory study evaluated whether intraperitoneal metformin administration during the neonatal period alters adult metabolic responses to hyperlipidic diet (HL) exposure in Wistar rats. Following weaning and sex determination, male offspring (n = 80) were included in the study and distributed among four experimental groups, i.e., saline\u2013normolipidic (SAL-NL), saline\u2013high-fat (SAL-HL), metformin\u2013normolipidic (MET-NL), and metformin\u2013high-fat (MET-HL), with 20 animals per group. From postnatal days 1 to 12, animals received daily intraperitoneal saline or metformin (100 mg\/kg\/day). From days 60 to 90, animals were fed normolipidic or hyperlipidic diets. Body mass, food intake, glucose tolerance (GTT), and insulin tolerance (ITT) were assessed. Neonatal metformin exposure was associated with reduced body mass gain in MET-HL animals compared to SAL-HL, while food intake differed according to dietary condition. Metformin-treated animals also exhibited improved insulin sensitivity, reflected by higher kITT values, while no significant differences were observed in glucose tolerance. These preliminary findings suggest that neonatal metformin administration may influence adult metabolic responses to dietary challenge. Further studies are required to elucidate the mechanisms and long-term implications of this early-life intervention.<\/jats:p>","DOI":"10.3390\/life16091398","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:20:43Z","timestamp":1787577643000},"page":"1398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal Metformin Exposure Is Associated with Altered Adult Metabolic Responses to Hyperlipidic Diet in Male Wistar Rats"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2640-8250","authenticated-orcid":false,"given":"Gustavo Henrique Don\u00e1 Rodrigues","family":"Almeida","sequence":"first","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"},{"name":"Laboratory of Development and Innovation, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio Guilherme de Assis","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Fuzeti","family":"Candian","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scarlett Rodrigues","family":"Raposo","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Ferreira","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Victor","family":"Damin","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Marques","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Paulo","family":"Jacinto Saavedra","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas Lopes de","family":"Almeida","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"},{"name":"Department of Biochemistry, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro Martins de","family":"Freitas","sequence":"additional","affiliation":[{"name":"Multidisciplinary Institute of Health, Federal University of Bahia, Vit\u00f3ria da Conquista 45029-094, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Piovan","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"},{"name":"Department of Biochemistry, State University of West Paran\u00e1, Cascavel 85819-110, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo C\u00e9zar de Freitas","family":"Mathias","sequence":"additional","affiliation":[{"name":"Experimental Laboratory in DOHaD (LEx DOHaD), Graduate Program in Biological Sciences, State University of Maring\u00e1, Maring\u00e1 87020-900, PR, Brazil"},{"name":"Multidisciplinary Institute of Health, Federal University of Bahia, Vit\u00f3ria da Conquista 45029-094, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2025, September 08). 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