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Obesity downregulates lipid metabolism genes in first trimester placenta

Placentas of obese women have low mitochondrial β-oxidation of fatty acids (FA) and accumulate lipids in late pregnancy. This creates a lipotoxic environment, impairing placental efficiency. We hypothesized that placental FA metabolism is impaired in women with obesity from early pregnancy. We asses...

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Autores principales: Rasool, Aisha, Mahmoud, Taysir, Mathyk, Begum, Kaneko-Tarui, Tomoko, Roncari, Danielle, White, Katharine O., O’Tierney-Ginn, Perrie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653480/
https://www.ncbi.nlm.nih.gov/pubmed/36371454
http://dx.doi.org/10.1038/s41598-022-24040-9
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author Rasool, Aisha
Mahmoud, Taysir
Mathyk, Begum
Kaneko-Tarui, Tomoko
Roncari, Danielle
White, Katharine O.
O’Tierney-Ginn, Perrie
author_facet Rasool, Aisha
Mahmoud, Taysir
Mathyk, Begum
Kaneko-Tarui, Tomoko
Roncari, Danielle
White, Katharine O.
O’Tierney-Ginn, Perrie
author_sort Rasool, Aisha
collection PubMed
description Placentas of obese women have low mitochondrial β-oxidation of fatty acids (FA) and accumulate lipids in late pregnancy. This creates a lipotoxic environment, impairing placental efficiency. We hypothesized that placental FA metabolism is impaired in women with obesity from early pregnancy. We assessed expression of key regulators of FA metabolism in first trimester placentas of lean and obese women. Maternal fasting triglyceride and insulin levels were measured in plasma collected at the time of procedure. Expression of genes associated with FA oxidation (FAO; ACOX1, CPT2, AMPKα), FA uptake (LPL, LIPG, MFSD2A), FA synthesis (ACACA) and storage (PLIN2) were significantly reduced in placentas of obese compared to lean women. This effect was exacerbated in placentas of male fetuses. Placental ACOX1 protein was higher in women with obesity and correlated with maternal circulating triglycerides. The PPARα pathway was enriched for placental genes impacted by obesity, and PPARα antagonism significantly reduced (3)H-palmitate oxidation in 1(st) trimester placental explants. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy.
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spelling pubmed-96534802022-11-15 Obesity downregulates lipid metabolism genes in first trimester placenta Rasool, Aisha Mahmoud, Taysir Mathyk, Begum Kaneko-Tarui, Tomoko Roncari, Danielle White, Katharine O. O’Tierney-Ginn, Perrie Sci Rep Article Placentas of obese women have low mitochondrial β-oxidation of fatty acids (FA) and accumulate lipids in late pregnancy. This creates a lipotoxic environment, impairing placental efficiency. We hypothesized that placental FA metabolism is impaired in women with obesity from early pregnancy. We assessed expression of key regulators of FA metabolism in first trimester placentas of lean and obese women. Maternal fasting triglyceride and insulin levels were measured in plasma collected at the time of procedure. Expression of genes associated with FA oxidation (FAO; ACOX1, CPT2, AMPKα), FA uptake (LPL, LIPG, MFSD2A), FA synthesis (ACACA) and storage (PLIN2) were significantly reduced in placentas of obese compared to lean women. This effect was exacerbated in placentas of male fetuses. Placental ACOX1 protein was higher in women with obesity and correlated with maternal circulating triglycerides. The PPARα pathway was enriched for placental genes impacted by obesity, and PPARα antagonism significantly reduced (3)H-palmitate oxidation in 1(st) trimester placental explants. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy. Nature Publishing Group UK 2022-11-12 /pmc/articles/PMC9653480/ /pubmed/36371454 http://dx.doi.org/10.1038/s41598-022-24040-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rasool, Aisha
Mahmoud, Taysir
Mathyk, Begum
Kaneko-Tarui, Tomoko
Roncari, Danielle
White, Katharine O.
O’Tierney-Ginn, Perrie
Obesity downregulates lipid metabolism genes in first trimester placenta
title Obesity downregulates lipid metabolism genes in first trimester placenta
title_full Obesity downregulates lipid metabolism genes in first trimester placenta
title_fullStr Obesity downregulates lipid metabolism genes in first trimester placenta
title_full_unstemmed Obesity downregulates lipid metabolism genes in first trimester placenta
title_short Obesity downregulates lipid metabolism genes in first trimester placenta
title_sort obesity downregulates lipid metabolism genes in first trimester placenta
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653480/
https://www.ncbi.nlm.nih.gov/pubmed/36371454
http://dx.doi.org/10.1038/s41598-022-24040-9
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