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Maternal Lipid Metabolism Directs Fetal Liver Programming following Nutrient Stress

The extreme metabolic demands of pregnancy require coordinated metabolic adaptations between mother and fetus to balance fetal growth and maternal health with nutrient availability. To determine maternal and fetal contributions to metabolic flexibility during gestation, pregnant mice with genetic im...

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Autores principales: Bowman, Caitlyn E., Selen Alpergin, Ebru S., Cavagnini, Kyle, Smith, Danielle M., Scafidi, Susanna, Wolfgang, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896898/
https://www.ncbi.nlm.nih.gov/pubmed/31665641
http://dx.doi.org/10.1016/j.celrep.2019.09.053
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author Bowman, Caitlyn E.
Selen Alpergin, Ebru S.
Cavagnini, Kyle
Smith, Danielle M.
Scafidi, Susanna
Wolfgang, Michael J.
author_facet Bowman, Caitlyn E.
Selen Alpergin, Ebru S.
Cavagnini, Kyle
Smith, Danielle M.
Scafidi, Susanna
Wolfgang, Michael J.
author_sort Bowman, Caitlyn E.
collection PubMed
description The extreme metabolic demands of pregnancy require coordinated metabolic adaptations between mother and fetus to balance fetal growth and maternal health with nutrient availability. To determine maternal and fetal contributions to metabolic flexibility during gestation, pregnant mice with genetic impairments in mitochondrial carbohydrate and/or lipid metabolism were subjected to nutrient deprivation. The maternal fasting response initiates a fetal liver transcriptional program marked by upregulation of lipid- and peroxisome proliferator-activated receptor alpha (Pparα)-regulated genes. Impaired maternal lipid metabolism alters circulating lipid metabolite concentrations and enhances the fetal response to fasting, which is largely dependent on fetal Pparα. Maternal fasting also improves metabolic deficits in fetal carbohydrate metabolism by increasing the availability of alternative substrates. Impairment of both carbohydrate and lipid metabolism in pregnant dams further exacerbates the fetal liver transcriptional response to nutrient deprivation. Together, these data demonstrate a regulatory role for mitochondrial macronutrient metabolism in mediating maternal-fetal metabolic communication, particularly when nutrients are limited.
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spelling pubmed-68968982019-12-06 Maternal Lipid Metabolism Directs Fetal Liver Programming following Nutrient Stress Bowman, Caitlyn E. Selen Alpergin, Ebru S. Cavagnini, Kyle Smith, Danielle M. Scafidi, Susanna Wolfgang, Michael J. Cell Rep Article The extreme metabolic demands of pregnancy require coordinated metabolic adaptations between mother and fetus to balance fetal growth and maternal health with nutrient availability. To determine maternal and fetal contributions to metabolic flexibility during gestation, pregnant mice with genetic impairments in mitochondrial carbohydrate and/or lipid metabolism were subjected to nutrient deprivation. The maternal fasting response initiates a fetal liver transcriptional program marked by upregulation of lipid- and peroxisome proliferator-activated receptor alpha (Pparα)-regulated genes. Impaired maternal lipid metabolism alters circulating lipid metabolite concentrations and enhances the fetal response to fasting, which is largely dependent on fetal Pparα. Maternal fasting also improves metabolic deficits in fetal carbohydrate metabolism by increasing the availability of alternative substrates. Impairment of both carbohydrate and lipid metabolism in pregnant dams further exacerbates the fetal liver transcriptional response to nutrient deprivation. Together, these data demonstrate a regulatory role for mitochondrial macronutrient metabolism in mediating maternal-fetal metabolic communication, particularly when nutrients are limited. 2019-10-29 /pmc/articles/PMC6896898/ /pubmed/31665641 http://dx.doi.org/10.1016/j.celrep.2019.09.053 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Bowman, Caitlyn E.
Selen Alpergin, Ebru S.
Cavagnini, Kyle
Smith, Danielle M.
Scafidi, Susanna
Wolfgang, Michael J.
Maternal Lipid Metabolism Directs Fetal Liver Programming following Nutrient Stress
title Maternal Lipid Metabolism Directs Fetal Liver Programming following Nutrient Stress
title_full Maternal Lipid Metabolism Directs Fetal Liver Programming following Nutrient Stress
title_fullStr Maternal Lipid Metabolism Directs Fetal Liver Programming following Nutrient Stress
title_full_unstemmed Maternal Lipid Metabolism Directs Fetal Liver Programming following Nutrient Stress
title_short Maternal Lipid Metabolism Directs Fetal Liver Programming following Nutrient Stress
title_sort maternal lipid metabolism directs fetal liver programming following nutrient stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896898/
https://www.ncbi.nlm.nih.gov/pubmed/31665641
http://dx.doi.org/10.1016/j.celrep.2019.09.053
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