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

Marika Charalambous*, Risha Amarsi, Catherine Williamson, Alice Mitchell, Samuel Furse, Albert Koulman, Mary A M Cleaton, Anne C. Ferguson-Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 metabolismallowed us to describe maternal hepatic adaptations required to provide LC-PUFAs to the developing fetus. We discovered a late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway which dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduced LC-PUFA accumulation by the fetus, specifically of docosahexaenoic acid (DHA), a critical nutrient for brain development.
Original languageEnglish
JournalNature Communications
Publication statusAccepted/In press - 19 Feb 2024

Fingerprint

Dive into the research topics of 'A co-ordinated transcriptional programme in the maternal liver supplies long chain polyunsaturated fatty acids to the conceptus using phospholipids'. Together they form a unique fingerprint.

Cite this