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Metabolism of 13C-labeled fatty acids in term human placental explants by liquid chromatography mass spectrometry

Metabolism of 13C-labeled fatty acids in term human placental explants by liquid chromatography mass spectrometry
Metabolism of 13C-labeled fatty acids in term human placental explants by liquid chromatography mass spectrometry

Placental lipid transport and metabolism is poorly understood despite its importance for fetal development and life-long health. We aimed to explore fatty acid (FA) processing in human villous placental explants from seven uncomplicated term singleton pregnancies delivered by elective cesarean section. Explants were treated with stable-isotope labeled palmitic acid (13C-PA), oleic acid (13C-OA) or docosahexaenoic acid (13C-DHA) for 3, 24 or 48 hours. Stable isotope labeled lipids synthesised by placental explants from labelled FA were quantified, alongside endogenous unlabeled placental lipids, by liquid-chromatography mass-spectrometry. Labeled phosphatidylcholines (PC), triacylglycerols (TAG), and phosphatidylethanolamines were detected in explants, whilst labeled lysophosphatidylcholines were found in both explants and conditioned-media. 13C-PA was primarily directed into PC synthesis (74% of 13C-PA-labeled lipids), while 13C-OA was directed almost equally into PC and TAG synthesis (45% and 53%, respectively, of 13C-OA-labeled lipids). 13C-DHA was only detectable in TAGs. TAGs demonstrated the highest isotopic enrichment for all 13C-FAs with 13C-OA-TAGs comprising >50% of total OA-TAGs (unlabelled and labeled); consistent with TAGs being a labile and accessible reservoir for FA storage. Variations in lipid incorporation were correlated to maternal glycemia and BMI suggesting that this experimental model could be used to investigate the effect of maternal factors on placental lipid metabolism. We conclude that lipid metabolic partitioning of freshly-imported FAs into labile and less labile lipid reservoirs in placenta is FA-dependent. This process may partly mediate the physiological preferential transplacental transfer of particular FAs to the fetus, but may also be implicated in the fetoplacental pathophysiology of maternal metabolic dysfunction.

0013-7227
Watkins, Oliver C.
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Islam, Mohammad Omedul
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Selvam, Preben
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Pillai, Reshma Appukuttan
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Cazenave-Gassiot, Amaury
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Bendt, Anne K.
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Karnani, Neerja
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Godfrey, Keith M.
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Lewis, Rohan M.
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Wenk, Markus R.
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Chan, Shiao-Yng
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Watkins, Oliver C.
985df9b8-72d6-4f32-9ee3-54553c990fdc
Islam, Mohammad Omedul
ad03e619-efac-49f3-b028-9d446697de74
Selvam, Preben
989ffd8a-e214-43b5-a3ce-a814fc491ee7
Pillai, Reshma Appukuttan
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Cazenave-Gassiot, Amaury
6eace962-dff6-4759-a8bf-090212014f9a
Bendt, Anne K.
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Karnani, Neerja
f4d4879d-3be1-4d6d-8d37-48af1035a4cf
Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Lewis, Rohan M.
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Wenk, Markus R.
d1ba356f-b0ed-4318-886a-c8f929679060
Chan, Shiao-Yng
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Watkins, Oliver C., Islam, Mohammad Omedul, Selvam, Preben, Pillai, Reshma Appukuttan, Cazenave-Gassiot, Amaury, Bendt, Anne K., Karnani, Neerja, Godfrey, Keith M., Lewis, Rohan M., Wenk, Markus R. and Chan, Shiao-Yng (2019) Metabolism of 13C-labeled fatty acids in term human placental explants by liquid chromatography mass spectrometry. Endocrinology. (doi:10.1210/en.2018-01020).

Record type: Article

Abstract

Placental lipid transport and metabolism is poorly understood despite its importance for fetal development and life-long health. We aimed to explore fatty acid (FA) processing in human villous placental explants from seven uncomplicated term singleton pregnancies delivered by elective cesarean section. Explants were treated with stable-isotope labeled palmitic acid (13C-PA), oleic acid (13C-OA) or docosahexaenoic acid (13C-DHA) for 3, 24 or 48 hours. Stable isotope labeled lipids synthesised by placental explants from labelled FA were quantified, alongside endogenous unlabeled placental lipids, by liquid-chromatography mass-spectrometry. Labeled phosphatidylcholines (PC), triacylglycerols (TAG), and phosphatidylethanolamines were detected in explants, whilst labeled lysophosphatidylcholines were found in both explants and conditioned-media. 13C-PA was primarily directed into PC synthesis (74% of 13C-PA-labeled lipids), while 13C-OA was directed almost equally into PC and TAG synthesis (45% and 53%, respectively, of 13C-OA-labeled lipids). 13C-DHA was only detectable in TAGs. TAGs demonstrated the highest isotopic enrichment for all 13C-FAs with 13C-OA-TAGs comprising >50% of total OA-TAGs (unlabelled and labeled); consistent with TAGs being a labile and accessible reservoir for FA storage. Variations in lipid incorporation were correlated to maternal glycemia and BMI suggesting that this experimental model could be used to investigate the effect of maternal factors on placental lipid metabolism. We conclude that lipid metabolic partitioning of freshly-imported FAs into labile and less labile lipid reservoirs in placenta is FA-dependent. This process may partly mediate the physiological preferential transplacental transfer of particular FAs to the fetus, but may also be implicated in the fetoplacental pathophysiology of maternal metabolic dysfunction.

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Myoinositol alters placental 13C-labelled fatty acid metabolism_O_C_Watkins_final - Accepted Manuscript
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Accepted/In Press date: 21 March 2019
e-pub ahead of print date: 28 March 2019

Identifiers

Local EPrints ID: 430251
URI: http://eprints.soton.ac.uk/id/eprint/430251
ISSN: 0013-7227
PURE UUID: 7b372d28-225f-4885-84e8-f01866fe81b4
ORCID for Keith M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Rohan M. Lewis: ORCID iD orcid.org/0000-0003-4044-9104

Catalogue record

Date deposited: 23 Apr 2019 16:30
Last modified: 10 Jan 2022 05:35

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Contributors

Author: Oliver C. Watkins
Author: Mohammad Omedul Islam
Author: Preben Selvam
Author: Reshma Appukuttan Pillai
Author: Amaury Cazenave-Gassiot
Author: Anne K. Bendt
Author: Neerja Karnani
Author: Rohan M. Lewis ORCID iD
Author: Markus R. Wenk
Author: Shiao-Yng Chan

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