A co-ordinated transcriptional programme in the maternal liver supplies long chain polyunsaturated fatty acids to the conceptus using phospholipids

Risha Amarsi, Samuel Furse, Mary A. M. Cleaton, Sarah Maurel, Alice L. Mitchell, Anne C. Ferguson-Smith, Nicolas Cenac, Catherine Williamson, Albert Koulman and Marika Charalambous ()
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Risha Amarsi: Faculty of Life Sciences and Medicine, King’s College London
Samuel Furse: Richmond
Mary A. M. Cleaton: University of Cambridge
Sarah Maurel: UPS
Alice L. Mitchell: King’s College London, Guy’s Campus
Anne C. Ferguson-Smith: University of Cambridge
Nicolas Cenac: UPS
Catherine Williamson: King’s College London, Guy’s Campus
Albert Koulman: University of Cambridge, Addenbrooke’s Treatment Centre, Keith Day Road
Marika Charalambous: Faculty of Life Sciences and Medicine, King’s College London

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract The long and very long chain polyunsaturated fatty acids (LC-PUFAs) are preferentially transported by the mother to the fetus. Failure to supply LC-PUFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary fatty acid intake and the molecular mechanisms of maternal supply. Here we employ a comprehensive approach combining untargeted and targeted lipidomics with transcriptional profiling of maternal and fetal tissues in mouse pregnancy. Comparison of wild-type mice with genetic models of impaired lipid metabolism allows us to describe maternal hepatic adaptations required to provide LC-PUFAs to the developing fetus. A late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduces LC-PUFA accumulation by the fetus, specifically of docosahexaenoic acid (DHA), a critical nutrient for brain development.

Date: 2024
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DOI: 10.1038/s41467-024-51089-z

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