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A co-ordinated transcriptional programme in the maternal liver supplies long chain polyunsaturated fatty acids to the conceptus using phospholipids
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Title: | A co-ordinated transcriptional programme in the maternal liver supplies long chain polyunsaturated fatty acids to the conceptus using phospholipids |
Authors: | Amarsi, R Furse, S Cleaton, MAM Maurel, S Mitchell, AL Ferguson-Smith, AC Cenac, N Williamson, C Koulman, A Charalambous, M |
Item Type: | Journal Article |
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. |
Issue Date: | 8-Aug-2024 |
Date of Acceptance: | 29-Jul-2024 |
URI: | http://hdl.handle.net/10044/1/114470 |
DOI: | 10.1038/s41467-024-51089-z |
ISSN: | 2041-1723 |
Publisher: | Nature Portfolio |
Journal / Book Title: | Nature Communications |
Volume: | 15 |
Copyright Statement: | © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Publication Status: | Published |
Conference Place: | England |
Article Number: | 6767 |
Online Publication Date: | 2024-08-08 |
Appears in Collections: | Department of Metabolism, Digestion and Reproduction Faculty of Medicine |
This item is licensed under a Creative Commons License