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These effects depend on the timing, intensity, and duration of exposure, and are proposed to be the cause or contribute to chronic adult disorders. Recent studies have proposed that artificial non-nutritive sweeteners (NNS), such as saccharin, can be included as one of these developmental disruptors. Saccharin consumption during pregnancy is strongly discouraged, as it can cross through the placenta and accumulate in the fetus, potentially impacting metabolic control for life. However, the mechanisms underlying the metabolic syndrome induced by maternal NNS consumption during pregnancy are not well understood. Some studies suggest that NNS may affect sweet taste receptors in the adult\u2019s guts, leading to changes in the release of glucagon-like peptide-1 (GLP-1) and insulin. The objective of the study is to investigate whether maternal saccharin consumption during pregnancy affects the gut-brain connection, leading to alterations in insulin\/GLP-1 signaling during neurodevelopment until adolescence.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Pregnant rats were administered 0.1% saccharin in drinking water throughout gestation, and the main components of the insulin\/GLP-1 signaling pathway were analyzed in the plasma, small intestine and hypothalamus of the offspring after weaning. Perinatal exposure to saccharin was linked to disrupted glucose homeostasis and insulin sensitivity in both male and female offspring.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We identified sex-dependent mechanisms that affected GLP-1 signaling in the intestine, associated with the expression of taste receptors and glucose transporters. These alterations affected the gut-brain axis and disrupted hypothalamic signaling associated with glucose regulation and food intake, primarily involving the GLP-1, leptin, and insulin signaling pathways.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These results suggest that developmental NNS exposure might contribute to the growing alteration in energy metabolism.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13293-025-00724-5","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T12:31:08Z","timestamp":1750077068000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gestational saccharin consumption disrupts gut-brain axis glucose homeostasis control in adolescent offspring rats in a sex-dependent manner"],"prefix":"10.1186","volume":"16","author":[{"given":"Beatriz","family":"Pacheco-S\u00e1nchez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Melgar-Locatelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"L\u00f3pez-Merch\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Ben\u00edtez-Mar\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Blasco-Alonso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesto","family":"Gonz\u00e1lez-Mesa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n","family":"Tovar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Rubio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Su\u00e1rez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Sanjuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Rodr\u00edguez","family":"de Fonseca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Al\u00e9n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marialuisa","family":"de Ceglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Rivera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"724_CR1","first-page":"124","volume":"32","author":"D Camacho-Buenrostro","year":"2015","unstructured":"Camacho-Buenrostro D, P\u00e9rez-Molina J, V\u00e1squez-Garibay EM, Panduro-Bar\u00f3n JG. 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This manuscript involves the use of animal data and tissue. All animal procedures were conducted in strict adherence to ARRIVE guidelines and the principles of laboratory animal care (National Research Council, Neuroscience CoGftUoAi, Research B, 2003) following the European Community Council Directive (63\/2010\/UE) and the Spanish Directive (RD52\/2013). All animal procedures were approved by the Ethical Committee of the Complutense University of Madrid (PSI-2012-35388; January 2012).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}