{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:10:49Z","timestamp":1774926649059,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NRFI2015\u201005"],"award-info":[{"award-number":["NRFI2015\u201005"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Well\u2010regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with gestational diabetes (GDM). We hypothesized that such dysregulation might arise from increased maternofetal glucose, leptin or insulin concentrations present in GDM, and that dysregulated PA and OA lipid metabolism could be moderated by myo\u2010inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope\u2010labelled <jats:sup>13<\/jats:sup>C\u2010PA or <jats:sup>13<\/jats:sup>C\u2010OA for 48\u00a0h. Explants were treated with glucose (5, 10\u00a0m<jats:sc>m<\/jats:sc>) or leptin (13\u00a0n<jats:sc>m<\/jats:sc>) or insulin (150\u00a0n<jats:sc>m<\/jats:sc>) in combination with myo\u2010inositol (0.3, 30, 60\u00a0\u03bc<jats:sc>m<\/jats:sc>). Forty\u2010seven <jats:sup>13<\/jats:sup>C\u2010PA lipids and 37 <jats:sup>13<\/jats:sup>C\u2010OA lipids were measured by liquid chromatography\u2013mass spectrometry (LCMS). Compared with controls (5\u00a0m<jats:sc>m<\/jats:sc> glucose), glucose (10\u00a0m<jats:sc>m<\/jats:sc>) increased 19 <jats:sup>13<\/jats:sup>C\u2010OA lipids and nine <jats:sup>13<\/jats:sup>C\u2010PA lipids, but decreased <jats:sup>13<\/jats:sup>C\u2010OA phosphatidylethanolamine 38:5 and <jats:sup>13<\/jats:sup>C\u2010PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing <jats:sup>13<\/jats:sup>C\u2010OA acylcarnitine 18:1, and insulin increasing four <jats:sup>13<\/jats:sup>C\u2010PA triacylglycerides. Most glucose, leptin and insulin\u2010induced alterations in lipids were attenuated by co\u2010incubation with myo\u2010inositol (30 or 60\u00a0\u03bc<jats:sc>m<\/jats:sc>), with attenuation also occurring in all subgroups stratified by GDM status and fetal sex. However, glucose\u2010induced increases in acylcarnitine were not attenuated by myo\u2010inositol and were even exaggerated in some instances. Myo\u2010inositol therefore appears to generally act as a moderator, suppressing the perturbation of lipid metabolic processes by glucose, leptin and insulin in placenta <jats:italic>in vitro<\/jats:italic>. Whether myo\u2010inositol protects the fetus and pregnancy from unfavourable outcomes requires further research.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15690-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of <jats:sup>13<\/jats:sup>C\u2010lipids from <jats:sup>13<\/jats:sup>C\u2010palmitic acid (PA) and <jats:sup>13<\/jats:sup>C\u2010oleic acid (OA) <jats:italic>in vitro<\/jats:italic> compared with untreated controls from the same placenta.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Co\u2010incubation with myo\u2010inositol attenuated most alterations induced by glucose, insulin or leptin in <jats:sup>13<\/jats:sup>C\u2010lipids, but did not affect alterations in <jats:sup>13<\/jats:sup>C\u2010acylcarnitines.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Alterations induced by glucose and leptin in <jats:sup>13<\/jats:sup>C\u2010PA triacylglycerides and <jats:sup>13<\/jats:sup>C\u2010PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo\u2010inositol co\u2010incubation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Insulin differently affected <jats:sup>13<\/jats:sup>C\u2010PA triacylglycerides and <jats:sup>13<\/jats:sup>C\u2010PA phospholipids depending on fetal sex, with alterations also attenuated by myo\u2010inositol co\u2010incubation.\n<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285036","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T09:22:19Z","timestamp":1692696139000},"page":"4151-4169","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Myo\u2010inositol alters the effects of glucose, leptin and insulin on placental palmitic acid and oleic acid metabolism"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-6412","authenticated-orcid":false,"given":"Oliver C.","family":"Watkins","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2362-2825","authenticated-orcid":false,"given":"Reshma Appukuttan","family":"Pillai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preben","family":"Selvam","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah E.J.","family":"Yong","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences Agency for Science, Technology and Research  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria K.B.","family":"Cracknell\u2010Hazra","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine National University of Singapore  Singapore"},{"name":"Singapore Institute 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