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To begin to understand how folic acid impacts metabolic health during pregnancy, we determined the effects of excess folic acid supplementation (5\u00d7 recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL\/6J) model of diet\u2010induced diabetes in pregnancy (western diet) and control mice, we show that folic acid supplementation improved insulin sensitivity in the female mice fed the western diet and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation are not due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (western and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex\u2010specific hepatic gene expression profiles were observed in the fetal offspring from supplemented dams but this differed between western and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype and has sex\u2010specific effects on offspring pancreas and liver.<\/jats:p>","DOI":"10.1096\/fj.202301491r","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T12:42:34Z","timestamp":1695991354000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Folic acid supplementation in a mouse model of diabetes in pregnancy alters insulin sensitivity in female mice and beta cell mass in offspring"],"prefix":"10.1096","volume":"37","author":[{"given":"Ei\u2010Xia","family":"Mussai","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of British Columbia  Vancouver British Columbia Canada"},{"name":"BC Children's Hospital Research Institute  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe A.","family":"Lofft","sequence":"additional","affiliation":[{"name":"BC Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Department of Pediatrics The University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Vanderkruk","sequence":"additional","affiliation":[{"name":"BC Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Department of Surgery The University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicha","family":"Boonpattrawong","sequence":"additional","affiliation":[{"name":"BC Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Department of Pediatrics The University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9126-0224","authenticated-orcid":false,"given":"Joshua W.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Rutgers University, The State University of New Jersey  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Rutgers University, The State University of New Jersey  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-7551","authenticated-orcid":false,"given":"Teodoro","family":"Bottiglieri","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1390-6587","authenticated-orcid":false,"given":"Angela M.","family":"Devlin","sequence":"additional","affiliation":[{"name":"BC Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Department of Pediatrics The University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"S233","article-title":"Diabetes and pregnancy. 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