Placental mobilization of free fatty acids contributes to altered materno-fetal transfer in obesity

BACKGROUND: Metabolic changes in obese pregnant women, such as changes of plasma lipids beyond physiological levels, may subsequently affect fetal development in utero. These metabolic derangements may remain in the offspring and continue throughout life. The placenta mediates bidirectional exchange of nutrients between mother and fetus. The impact of prepregnancy obesity on placental transfer of lipids is still unknown.

OBJECTIVE: We aimed to examine materno-to-fetal free fatty acid (FFA) transfer by a combined experimental and modeling approach. Flux of 13C-labeled FFA was evaluated by ex vivo perfusion of human placentae as a function of prepregnancy obesity. Mathematical modeling complemented ex vivo results by providing FFA kinetic parameters.

RESULTS: Obesity was strongly associated with elevated materno-to-fetal transfer of applied 13C-FFA. Clearance of polyunsaturated 13C-docosahexaenoic acid (DHA) was most prominently affected. The use of the mathematical model revealed a lower tissue storage capacity for DHA in obese compared with lean placentae.

CONCLUSION: Besides direct materno-to-fetal FFA transfer, placental mobilization accounts for the fetal FA supply. Together, with metabolic changes in the mother and an elevated materno-fetal FFA transfer shown in obesity, these changes suggest that they may be transmitted to the fetus, with yet unknown consequences.

10.1038/s41366-021-00781-x

0307-0565

1114-1123

Hirschmugl, Birgit

ca692409-549c-4419-b156-de715423d688

Perazzolo, Simone

bc5e3f83-6eb6-4ed6-9173-860a2d03817d

Sengers, Bram G

d6b771b1-4ede-48c5-9644-fa86503941aa

Lewis, Rohan M

caaeb97d-ea69-4f7b-8adb-5fa25e2d3502

Gruber, Michael

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Desoye, Gernot

905d057f-c298-423a-9244-78b789ecdd68

Wadsack, Christian

dd320713-7a3a-4049-85fe-dfe0193d838c

May 2021

Hirschmugl, Birgit

ca692409-549c-4419-b156-de715423d688

Perazzolo, Simone

bc5e3f83-6eb6-4ed6-9173-860a2d03817d

Sengers, Bram G

d6b771b1-4ede-48c5-9644-fa86503941aa

Lewis, Rohan M

caaeb97d-ea69-4f7b-8adb-5fa25e2d3502

Gruber, Michael

00eb5813-72f4-4a48-90d5-077d08bc0284

Desoye, Gernot

905d057f-c298-423a-9244-78b789ecdd68

Wadsack, Christian

dd320713-7a3a-4049-85fe-dfe0193d838c

Hirschmugl, Birgit, Perazzolo, Simone, Sengers, Bram G, Lewis, Rohan M, Gruber, Michael, Desoye, Gernot and Wadsack, Christian (2021) Placental mobilization of free fatty acids contributes to altered materno-fetal transfer in obesity. International Journal of Obesity, 45 (5), 1114-1123. (doi:10.1038/s41366-021-00781-x).

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Accepted/In Press date: 1 February 2021

e-pub ahead of print date: 26 February 2021

Published date: May 2021

Additional Information: Funding Information: Acknowledgements GC–MS analysis was performed with the help and guidance of Harald Köfeler, PhD and Stefanie Rappold from the Core Facility for Mass Spectrometry, Center for Medical Research, Medical University of Graz, Austria. We want to thank Bettina Amtmann and Petra Winkler for communication between research laboratory and delivery room and Susanne Kopp for technical assistance. This work was funded by European Union’s Seventh Framework Program (FP7/ 2007–2013), project Early Nutrition under grant agreement n°289346. Birgit Hirschmugl received funding from the Anniversary Fund of the Oesterreichiche Nationalbank (grant no. 18181) and the Medical University of Graz by the PhD Program Molecular Fundamentals of Inflammation (DK-MOLIN, funded by the Austrian Science Fund FWF (W1241)). This work was further supported by Soroptimist International, Club Goldes Südsteiermark. Simone Perazzolo received funding from the Institute of Life Sciences, Southampton. Publisher Copyright: © 2021, The Author(s).