In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women

Antonio Gázquez, María T. Prieto-Sánchez, José E. Blanco-Carnero, Dewi van Harskamp, Simone Perazzolo, J. Efraim Oosterink, Hans Demmelmair, Henk Schierbeek, Bram G. Sengers, Rohan M. Lewis, Johannes B. van Goudoever, Berthold Koletzko, Elvira Larqué

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Key points: Placental structure and function can be modified as a result of maternal obesity affecting materno-fetal fatty acids (FA) transport. We report for the first time, in humans and in vivo, the kinetics of placental FA transfer in normo-weight and in normolipemic obese pregnant women using stable isotopes. The administration of different tracer FA with similar behaviour to the mother at different time points allows the collection of kinetic information on materno-fetal transfer of FA despite only one sample of placenta and cord can be collected per subject. Computational modelling showed a good fit to the data when considering all maternal plasma lipid classes but not when based only on non-esterified FA. The novel approach using multiple tracer FA administration combined with computational modelling shows a consistent time course of placental tracer FA and predicted total FA accumulation. Abstract: We analyse for the first time the in vivo materno-fetal kinetic transfer of fatty acids (FA) labelled with stable isotopes in control and obese (OB) pregnant women. Labelled FA with a similar metabolism (stearic acid: 13C-SA; palmitic acid: 13C-PA; oleic acid: 13C-OA) were orally administered at −4 h, −8 h and −12 h, respectively prior to elective caesarean section to 10 pregnant women with a body mass index >30 (OB) and 10 with a body mass index in the range 20–25 (NW). Placenta, venous and arterial cord blood were collected obtaining a wide range of FA enrichments. A combined experimental and computational modelling analysis was applied. FA fractional synthesis rate (FSR) in placenta was 11–12% h–1. No differences were observed between NW and normo-lipidemic OB. It was not possible to estimate FA FSR in cord blood with this oral bolus dose approach. Computational modelling demonstrated a good fit to the data when all maternal plasma lipid classes were included but not with modelling based only on the non-esterified FA fraction. The estimated materno-fetal 13C-FA transfer was ∼1%. In conclusion, our approach using multiple 13C-FA tracers allowed us to estimated FSR in placental/maternal plasma but not in fetal/maternal compartments. Computational modelling showed a consistent time course of placental 13C-FA transfer and predicted total fetal FA accumulation during the experiment. We conclude that, in addition to non-esterified FA fraction in the maternal circulation, maternal plasma very low-density lipoprotein and other lipoproteins are important contributors to placental FA transfer to the fetus.
Original languageEnglish
Pages (from-to)4959-4973
Number of pages15
JournalJournal of Physiology
Volume597
Issue number19
DOIs
Publication statusPublished - 1 Oct 2019
Externally publishedYes

Cite this

Gázquez, A., Prieto-Sánchez, M. T., Blanco-Carnero, J. E., van Harskamp, D., Perazzolo, S., Oosterink, J. E., ... Larqué, E. (2019). In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women. Journal of Physiology, 597(19), 4959-4973. https://doi.org/10.1113/JP278146
Gázquez, Antonio ; Prieto-Sánchez, María T. ; Blanco-Carnero, José E. ; van Harskamp, Dewi ; Perazzolo, Simone ; Oosterink, J. Efraim ; Demmelmair, Hans ; Schierbeek, Henk ; Sengers, Bram G. ; Lewis, Rohan M. ; van Goudoever, Johannes B. ; Koletzko, Berthold ; Larqué, Elvira. / In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women. In: Journal of Physiology. 2019 ; Vol. 597, No. 19. pp. 4959-4973.
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abstract = "Key points: Placental structure and function can be modified as a result of maternal obesity affecting materno-fetal fatty acids (FA) transport. We report for the first time, in humans and in vivo, the kinetics of placental FA transfer in normo-weight and in normolipemic obese pregnant women using stable isotopes. The administration of different tracer FA with similar behaviour to the mother at different time points allows the collection of kinetic information on materno-fetal transfer of FA despite only one sample of placenta and cord can be collected per subject. Computational modelling showed a good fit to the data when considering all maternal plasma lipid classes but not when based only on non-esterified FA. The novel approach using multiple tracer FA administration combined with computational modelling shows a consistent time course of placental tracer FA and predicted total FA accumulation. Abstract: We analyse for the first time the in vivo materno-fetal kinetic transfer of fatty acids (FA) labelled with stable isotopes in control and obese (OB) pregnant women. Labelled FA with a similar metabolism (stearic acid: 13C-SA; palmitic acid: 13C-PA; oleic acid: 13C-OA) were orally administered at −4 h, −8 h and −12 h, respectively prior to elective caesarean section to 10 pregnant women with a body mass index >30 (OB) and 10 with a body mass index in the range 20–25 (NW). Placenta, venous and arterial cord blood were collected obtaining a wide range of FA enrichments. A combined experimental and computational modelling analysis was applied. FA fractional synthesis rate (FSR) in placenta was 11–12{\%} h–1. No differences were observed between NW and normo-lipidemic OB. It was not possible to estimate FA FSR in cord blood with this oral bolus dose approach. Computational modelling demonstrated a good fit to the data when all maternal plasma lipid classes were included but not with modelling based only on the non-esterified FA fraction. The estimated materno-fetal 13C-FA transfer was ∼1{\%}. In conclusion, our approach using multiple 13C-FA tracers allowed us to estimated FSR in placental/maternal plasma but not in fetal/maternal compartments. Computational modelling showed a consistent time course of placental 13C-FA transfer and predicted total fetal FA accumulation during the experiment. We conclude that, in addition to non-esterified FA fraction in the maternal circulation, maternal plasma very low-density lipoprotein and other lipoproteins are important contributors to placental FA transfer to the fetus.",
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Gázquez, A, Prieto-Sánchez, MT, Blanco-Carnero, JE, van Harskamp, D, Perazzolo, S, Oosterink, JE, Demmelmair, H, Schierbeek, H, Sengers, BG, Lewis, RM, van Goudoever, JB, Koletzko, B & Larqué, E 2019, 'In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women' Journal of Physiology, vol. 597, no. 19, pp. 4959-4973. https://doi.org/10.1113/JP278146

In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women. / Gázquez, Antonio; Prieto-Sánchez, María T.; Blanco-Carnero, José E.; van Harskamp, Dewi; Perazzolo, Simone; Oosterink, J. Efraim; Demmelmair, Hans; Schierbeek, Henk; Sengers, Bram G.; Lewis, Rohan M.; van Goudoever, Johannes B.; Koletzko, Berthold; Larqué, Elvira.

In: Journal of Physiology, Vol. 597, No. 19, 01.10.2019, p. 4959-4973.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women

AU - Gázquez, Antonio

AU - Prieto-Sánchez, María T.

AU - Blanco-Carnero, José E.

AU - van Harskamp, Dewi

AU - Perazzolo, Simone

AU - Oosterink, J. Efraim

AU - Demmelmair, Hans

AU - Schierbeek, Henk

AU - Sengers, Bram G.

AU - Lewis, Rohan M.

AU - van Goudoever, Johannes B.

AU - Koletzko, Berthold

AU - Larqué, Elvira

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Key points: Placental structure and function can be modified as a result of maternal obesity affecting materno-fetal fatty acids (FA) transport. We report for the first time, in humans and in vivo, the kinetics of placental FA transfer in normo-weight and in normolipemic obese pregnant women using stable isotopes. The administration of different tracer FA with similar behaviour to the mother at different time points allows the collection of kinetic information on materno-fetal transfer of FA despite only one sample of placenta and cord can be collected per subject. Computational modelling showed a good fit to the data when considering all maternal plasma lipid classes but not when based only on non-esterified FA. The novel approach using multiple tracer FA administration combined with computational modelling shows a consistent time course of placental tracer FA and predicted total FA accumulation. Abstract: We analyse for the first time the in vivo materno-fetal kinetic transfer of fatty acids (FA) labelled with stable isotopes in control and obese (OB) pregnant women. Labelled FA with a similar metabolism (stearic acid: 13C-SA; palmitic acid: 13C-PA; oleic acid: 13C-OA) were orally administered at −4 h, −8 h and −12 h, respectively prior to elective caesarean section to 10 pregnant women with a body mass index >30 (OB) and 10 with a body mass index in the range 20–25 (NW). Placenta, venous and arterial cord blood were collected obtaining a wide range of FA enrichments. A combined experimental and computational modelling analysis was applied. FA fractional synthesis rate (FSR) in placenta was 11–12% h–1. No differences were observed between NW and normo-lipidemic OB. It was not possible to estimate FA FSR in cord blood with this oral bolus dose approach. Computational modelling demonstrated a good fit to the data when all maternal plasma lipid classes were included but not with modelling based only on the non-esterified FA fraction. The estimated materno-fetal 13C-FA transfer was ∼1%. In conclusion, our approach using multiple 13C-FA tracers allowed us to estimated FSR in placental/maternal plasma but not in fetal/maternal compartments. Computational modelling showed a consistent time course of placental 13C-FA transfer and predicted total fetal FA accumulation during the experiment. We conclude that, in addition to non-esterified FA fraction in the maternal circulation, maternal plasma very low-density lipoprotein and other lipoproteins are important contributors to placental FA transfer to the fetus.

AB - Key points: Placental structure and function can be modified as a result of maternal obesity affecting materno-fetal fatty acids (FA) transport. We report for the first time, in humans and in vivo, the kinetics of placental FA transfer in normo-weight and in normolipemic obese pregnant women using stable isotopes. The administration of different tracer FA with similar behaviour to the mother at different time points allows the collection of kinetic information on materno-fetal transfer of FA despite only one sample of placenta and cord can be collected per subject. Computational modelling showed a good fit to the data when considering all maternal plasma lipid classes but not when based only on non-esterified FA. The novel approach using multiple tracer FA administration combined with computational modelling shows a consistent time course of placental tracer FA and predicted total FA accumulation. Abstract: We analyse for the first time the in vivo materno-fetal kinetic transfer of fatty acids (FA) labelled with stable isotopes in control and obese (OB) pregnant women. Labelled FA with a similar metabolism (stearic acid: 13C-SA; palmitic acid: 13C-PA; oleic acid: 13C-OA) were orally administered at −4 h, −8 h and −12 h, respectively prior to elective caesarean section to 10 pregnant women with a body mass index >30 (OB) and 10 with a body mass index in the range 20–25 (NW). Placenta, venous and arterial cord blood were collected obtaining a wide range of FA enrichments. A combined experimental and computational modelling analysis was applied. FA fractional synthesis rate (FSR) in placenta was 11–12% h–1. No differences were observed between NW and normo-lipidemic OB. It was not possible to estimate FA FSR in cord blood with this oral bolus dose approach. Computational modelling demonstrated a good fit to the data when all maternal plasma lipid classes were included but not with modelling based only on the non-esterified FA fraction. The estimated materno-fetal 13C-FA transfer was ∼1%. In conclusion, our approach using multiple 13C-FA tracers allowed us to estimated FSR in placental/maternal plasma but not in fetal/maternal compartments. Computational modelling showed a consistent time course of placental 13C-FA transfer and predicted total fetal FA accumulation during the experiment. We conclude that, in addition to non-esterified FA fraction in the maternal circulation, maternal plasma very low-density lipoprotein and other lipoproteins are important contributors to placental FA transfer to the fetus.

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Gázquez A, Prieto-Sánchez MT, Blanco-Carnero JE, van Harskamp D, Perazzolo S, Oosterink JE et al. In vivo kinetic study of materno-fetal fatty acid transfer in obese and normal weight pregnant women. Journal of Physiology. 2019 Oct 1;597(19):4959-4973. https://doi.org/10.1113/JP278146