Sex-specific responses in placental fatty acid oxidation, esterification and transfer capacity to maternal obesity.

Abstract

Fatty acid metabolism and oxidation capacity in the placenta, which likely affects the rate and composition of lipid delivered to the fetus remains poorly understood. Long chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), are critical for fetal growth and brain development. We determined the impact of maternal obesity on placental fatty acid oxidation, esterification and transport capacity by measuring PhosphatidylCholine (PC) and LysoPhosphatidylCholine (LPC) containing DHA by mass spectrometry in mother-placenta-baby triads as well as placental free carnitine and acylcarnitine metabolites in women with normal and obese pre-pregnancy BMI. Placental protein expression of enzymes involved in beta-oxidation and esterification pathways, MFSD2a (lysophosphatidylcholine transporter) and OCTN2 (carnitine transporter) expression in syncytiotrophoblast microvillous (MVM) and basal (BM) membranes were determined by Western Blot. Maternal obesity was associated with decreased umbilical cord plasma DHA in LPC and PC fractions in male, but not female, fetuses. Basal membrane MFSD2a protein expression was increased in placenta of males of obese mothers. In female placentas, despite an increased MVM OCTN2 expression, maternal obesity was associated with a reduced MUFA-carnitine levels and increased esterification enzymes. We speculate that lower DHA-PL in fetal circulation of male offspring of obese mothers, despite a significant increase in transporter expression for LPC-DHA, may lead to low DHA needed for brain development contributing to neurological consequences that are more prevalent in male children. Female placentas likely have reduced beta-oxidation capacity and appear to store FA through greater placental esterification, suggesting impaired placenta function and lipid transfer in female placentas of obese mothers.

• Authors: Theresa L Powell, Kelsey Barner, Lana Madi, Michael Armstrong, Jonathan Manke, Charis Uhlson, Thomas Jansson, Véronique Ferchaud-Roucher
• Journal: Biochimica et biophysica acta. Molecular and cell biology of lipids (Biochim Biophys Acta Mol Cell Biol Lipids) Vol. 1866 Issue 3 Pg. 158861 (03 2021) ISSN: 1879-2618 [Electronic] Netherlands
• PMID: 33321178 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Fatty Acids

Topics

• Adult
• Esterification
• Fatty Acids (metabolism)
• Female
• Fetus (metabolism)
• Humans
• Male
• Maternal-Fetal Exchange
• Obesity, Maternal (metabolism)
• Oxidation-Reduction
• Placenta (metabolism)
• Pregnancy
• Sex Characteristics