Myo‐inositol alters the effects of glucose, leptin and insulin on placental palmitic acid and oleic acid metabolism

Myo‐inositol alters the effects of glucose, leptin and insulin on placental palmitic acid and oleic acid metabolism

The Journal of Physiology

10.1113/JP285036

https://doi.org/10.1113/jp285036

Oliver C. Watkins, Reshma Appukuttan Pillai, Preben Selvam, Hannah E.J. Yong, Victoria K.B. Cracknell‐Hazra, Neha Sharma, Amaury Cazenave‐Gassiot, Anne K. Bendt, Keith M. Godfrey, Rohan M. Lewis, Markus R. Wenk, Shiao‐Yng Chan

placenta, palmitic acid, oleic acid, lipid metabolism, Gestational diabetes

22 August 2023

Watkins, O. C., Pillai, R. A., Selvam, P., Yong, H. E. J., Cracknell‐Hazra, V. K. B., Sharma, N., Cazenave‐Gassiot, A., Bendt, A. K., Godfrey, K. M., Lewis, R. M., Wenk, M. R., & Chan, S. (2023). Myo‐inositol alters the effects of glucose, leptin and insulin on placental palmitic acid and oleic acid metabolism. The Journal of Physiology, 601(18), 4151–4169. Portico. https://doi.org/10.1113/jp285036

Well‐regulated 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‐inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope‐labelled 13C‐PA or 13C‐OA for 48 h. Explants were treated with glucose (5, 10 mm) or leptin (13 nm) or insulin (150 nm) in combination with myo‐inositol (0.3, 30, 60 μm). Forty‐seven 13C‐PA lipids and 37 13C‐OA lipids were measured by liquid chromatography–mass spectrometry (LCMS). Compared with controls (5 mm glucose), glucose (10 mm) increased 19 13C‐OA lipids and nine 13C‐PA lipids, but decreased 13C‐OA phosphatidylethanolamine 38:5 and 13C‐PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing 13C‐OA acylcarnitine 18:1, and insulin increasing four 13C‐PA triacylglycerides. Most glucose, leptin and insulin‐induced alterations in lipids were attenuated by co‐incubation with myo‐inositol (30 or 60 μm), with attenuation also occurring in all subgroups stratified by GDM status and fetal sex. However, glucose‐induced increases in acylcarnitine were not attenuated by myo‐inositol and were even exaggerated in some instances. Myo‐inositol therefore appears to generally act as a moderator, suppressing the perturbation of lipid metabolic processes by glucose, leptin and insulin in placenta in vitro. Whether myo‐inositol protects the fetus and pregnancy from unfavourable outcomes requires further research. imageKey points Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of 13C‐lipids from 13C‐palmitic acid (PA) and 13C‐oleic acid (OA) in vitro compared with untreated controls from the same placenta. Co‐incubation with myo‐inositol attenuated most alterations induced by glucose, insulin or leptin in 13C‐lipids, but did not affect alterations in 13C‐acylcarnitines. Alterations induced by glucose and leptin in 13C‐PA triacylglycerides and 13C‐PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo‐inositol co‐incubation. Insulin differently affected 13C‐PA triacylglycerides and 13C‐PA phospholipids depending on fetal sex, with alterations also attenuated by myo‐inositol co‐incubation.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research / project is supported by the Agency for Science, Technology and Research - Industry Alignment Fund – Industry Collaboration Projects
Grant Reference no. : I1901E0040

This research is supported by a Clinician Scientist Award awarded to SYC from the Singapore National Medical Research Council (NMRC/CSA-INV/0010/2016; MOH-000455). SYC and KMG are part of an academic consortium that has received research funding from Société des Produits Nestlé S.A. for work unrelated to this manuscript, and are co-inventors on patent filings by Nestlé S.A. which covers the use of inositol in human health applications but which do not draw on the work in this manuscript. KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG is supported by the UK Medical Research Council (MC_UU_12 011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515-10 042) and NIHR Southampton Biomedical Research Centre (IS-BRC-1215-20 004)), the European Union (Erasmus+ Programme ImpENSA 598 488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP) and the British Heart Foundation (RG/15/17/3174, SP/F/21/150 013). The Singapore Lipidomics Incubator receives funding from the Life Sciences Institute, the National University of Singapore Yong Loo Lin School of Medicine, the National Research Foundation Investigatorship (grant number NRFI2015-05) and A∗STAR (IAF-ICP I1901E0040). The other authors have no financial or personal conflict of interest to declare.

https://oar.a-star.edu.sg/communities-collections/articles/21983

0022-3751
1469-7793

Institute for Human Development and Potential

https://doi.org/10.1113/jp285036