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
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.
carnitine palmitoyltransferases, CPT1B, lipid metabolism, maternal age, obesity, overweight, placenta
Yong, Hannah E.J.
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Watkins, Oliver C.
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Mah, Tania Ken Lin
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Cracknell-Hazra, Victoria Kathryn Bonnell
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Pillai, Reshma Appukuttan
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Selvam, Preben
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Islam, Mohammad O.
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Sharma, Neha
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Cazenave-Gassiot, Amaury
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Bendt, Anne K.
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Wenk, Markus R.
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Godfrey, Keith
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Lewis, Rohan
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Chan, Shiao-Yng
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18 May 2023
Yong, Hannah E.J.
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Watkins, Oliver C.
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Mah, Tania Ken Lin
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Cracknell-Hazra, Victoria Kathryn Bonnell
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Pillai, Reshma Appukuttan
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Selvam, Preben
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Islam, Mohammad O.
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Sharma, Neha
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Cazenave-Gassiot, Amaury
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Bendt, Anne K.
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Wenk, Markus R.
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Godfrey, Keith
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Lewis, Rohan
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Chan, Shiao-Yng
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Yong, Hannah E.J., Watkins, Oliver C., Mah, Tania Ken Lin, Cracknell-Hazra, Victoria Kathryn Bonnell, Pillai, Reshma Appukuttan, Selvam, Preben, Islam, Mohammad O., Sharma, Neha, Cazenave-Gassiot, Amaury, Bendt, Anne K., Wenk, Markus R., Godfrey, Keith, Lewis, Rohan and Chan, Shiao-Yng
(2023)
Increasing maternal age associates with lower placental CPT1B mRNA expression and acylcarnitines, particularly in overweight women.
Frontiers in Physiology, 14, [1166827].
(doi:10.3389/fphys.2023.1166827).
Abstract
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.
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Frontiers maternal age and CPT accepted manuscript
- Accepted Manuscript
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fphys-14-1166827
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Accepted/In Press date: 4 May 2023
Published date: 18 May 2023
Additional Information:
Funding Information:
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 (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). For the purpose of Open Access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. Funders played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Publisher Copyright:
Copyright © 2023 Yong, Watkins, Mah, Cracknell-Hazra, Pillai, Selvam, Islam, Sharma, Cazenave-Gassiot, Bendt, Wenk, Godfrey, Lewis and Chan.
Keywords:
carnitine palmitoyltransferases, CPT1B, lipid metabolism, maternal age, obesity, overweight, placenta
Identifiers
Local EPrints ID: 477321
URI: http://eprints.soton.ac.uk/id/eprint/477321
ISSN: 1664-042X
PURE UUID: 42902583-f95b-4087-9578-63bd3215c92f
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Date deposited: 02 Jun 2023 17:22
Last modified: 15 Aug 2024 01:37
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Contributors
Author:
Hannah E.J. Yong
Author:
Oliver C. Watkins
Author:
Tania Ken Lin Mah
Author:
Victoria Kathryn Bonnell Cracknell-Hazra
Author:
Reshma Appukuttan Pillai
Author:
Preben Selvam
Author:
Mohammad O. Islam
Author:
Neha Sharma
Author:
Amaury Cazenave-Gassiot
Author:
Anne K. Bendt
Author:
Markus R. Wenk
Author:
Shiao-Yng Chan
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