Obesity downregulates lipid metabolism genes in first trimester placenta
Abstract 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....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24040-9 |
| _version_ | 1797988443638202368 |
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| author | Aisha Rasool Taysir Mahmoud Begum Mathyk Tomoko Kaneko-Tarui Danielle Roncari Katharine O. White Perrie O’Tierney-Ginn |
| author_facet | Aisha Rasool Taysir Mahmoud Begum Mathyk Tomoko Kaneko-Tarui Danielle Roncari Katharine O. White Perrie O’Tierney-Ginn |
| author_sort | Aisha Rasool |
| collection | DOAJ |
| description | Abstract 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 3H-palmitate oxidation in 1st trimester placental explants. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy. |
| first_indexed | 2024-04-11T08:04:11Z |
| format | Article |
| id | doaj.art-d8bf2539d3cb401fa897dc60f4d69779 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T08:04:11Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d8bf2539d3cb401fa897dc60f4d697792022-12-22T04:35:37ZengNature PortfolioScientific Reports2045-23222022-11-0112111310.1038/s41598-022-24040-9Obesity downregulates lipid metabolism genes in first trimester placentaAisha Rasool0Taysir Mahmoud1Begum Mathyk2Tomoko Kaneko-Tarui3Danielle Roncari4Katharine O. White5Perrie O’Tierney-Ginn6Tufts Medical Center, Mother Infant Research InstituteTufts Medical Center, Mother Infant Research InstituteBrandon Regional HospitalTufts Medical Center, Mother Infant Research InstituteDepartment of Obstetrics and Gynecology, Tufts University School of MedicineDepartment of Obstetrics and Gynecology, Boston University School of MedicineTufts Medical Center, Mother Infant Research InstituteAbstract 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 3H-palmitate oxidation in 1st trimester placental explants. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy.https://doi.org/10.1038/s41598-022-24040-9 |
| spellingShingle | Aisha Rasool Taysir Mahmoud Begum Mathyk Tomoko Kaneko-Tarui Danielle Roncari Katharine O. White Perrie O’Tierney-Ginn Obesity downregulates lipid metabolism genes in first trimester placenta Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-022-24040-9 |
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