Increasing maternal age associates with lower placental CPT1B mRNA expression and acylcarnitines, particularly in overweight women

Increasing maternal age associates with lower placental CPT1B mRNA expression and acylcarnitines, particularly in overweight women

Frontiers in Physiology

10.3389/fphys.2023.1166827

https://doi.org/10.3389/fphys.2023.1166827

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

placenta, lipid metabolism, maternal age, acylcarnitines

18 May 2023

Yong, H. E. J., Watkins, O. C., Mah, T. K. L., Cracknell-Hazra, V. K. B., Pillai, R. A., Selvam, P., Islam, M. O., Sharma, N., Cazenave-Gassiot, A., Bendt, A. K., Wenk, M. R., Godfrey, K. M., Lewis, R. M., & Chan, S.-Y. (2023). Increasing maternal age associates with lower placental CPT1B mRNA expression and acylcarnitines, particularly in overweight women. Frontiers in Physiology, 14. https://doi.org/10.3389/fphys.2023.1166827

Older pregnant women have increased risks of complications including gestational diabetes and stillbirth. Carnitine palmitoyl transferase (CPT) expression declines with age in several tissues and is linked with poorer metabolic health. Mitochondrial CPTs catalyze acylcarnitine synthesis, which facilitates fatty acid oxidization as fuel. We hypothesized that the placenta, containing maternally-inherited mitochondria, shows an age-related CPT decline that lowers placental acylcarnitine synthesis, increasing vulnerability to pregnancy complications. We assessed CPT1A, CPT1B, CPT1C and CPT2 mRNA expression by qPCR in 77 placentas and quantified 10 medium and long-chain acylcarnitines by LC-MS/MS in a subset of 50 placentas. Older maternal age associated with lower expression of placental CPT1B, but not CPT1A, CPT1C or CPT2. CPT1B expression positively associated with eight acylcarnitines and CPT1C with three acylcarnitines, CPT1A negatively associated with nine acylcarnitines, while CPT2 did not associate with any acylcarnitine. Older maternal age associated with reductions in five acylcarnitines, only in those with BMI≥ 25 kg/m2, and not after adjusting for CPT1B expression. Our findings suggest that CPT1B is the main transferase for placental long-chain acylcarnitine synthesis, and age-related CPT1B decline may underlie decreased placental metabolic flexibility, potentially contributing to pregnancy complications in older women, particularly if they are overweight.

Attribution 4.0 International (CC BY 4.0)

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-CSAINV19nov-0002), by the National University of Singapore, National University Health System Singapore and the Singapore Institute for Clinical Sciences A*STAR. 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 (NRFI 2015–05) and A*STAR (IAF-ICP I1901E0040). KMG is supported by the United Kingdom Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515–10042) and NIHR Southampton Biomedical Research Centre (NIHR203319)), the European Union (Erasmus + Programme ImpENSA 598488-EPP-1–2018-1-DE-EPPKA2-CBHE-JP), and the US National Institute On Aging of the National Institutes of Health (Award No. U24AG047867).

This research is supported by core funding from: Institute for Human Development and Potential
Grant Reference no. :

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

© 2023 Yong, Watkins, Mah, Cracknell-Hazra, Pillai, Selvam, Islam, Sharma,Cazenave-Gassiot, Bendt, Wenk,Godfrey, Lewis and Chan. This is an open-access article distributed under the termsof theCreative Commons AttributionLicense (CC BY). The use, distribution orreproduction in other forums ispermitted, provided the original author(s)and the copyright owner(s) are creditedand that the original publication in thisjournal is cited, in accordance withaccepted academic practice. No use,distribution or reproduction is permittedwhich does not comply with these terms. This paper was first published by Frontiers Media at https://doi.org/10.3389/fphys.2023.1166827

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Institute for Human Development and Potential

https://doi.org/10.3389/fphys.2023.1166827