Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis?
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1136/bmjdrc-2019-000923 http://hdl.handle.net/11449/228780 |
Resumo: | Introduction Gestational diabetes mellitus (GDM), a common pregnancy disorder, increases the risk of fetal overgrowth and later metabolic morbidity in the offspring. The placenta likely mediates these sequelae, but the exact mechanisms remain elusive. Mitochondrial dynamics refers to the joining and division of these organelles, in attempts to maintain cellular homeostasis in stress conditions or alterations in oxygen and fuel availability. These remodeling processes are critical to optimize mitochondrial function, and their disturbances characterize diabetes and obesity. Methods and results Herein we show that placental mitochondrial dynamics are tilted toward fusion in GDM, as evidenced by transmission electron microscopy and changes in the expression of key mechanochemical enzymes such as OPA1 and active phosphorylated DRP1. In vitro experiments using choriocarcinoma JEG-3 cells demonstrated that increased exposure to insulin, which typifies GDM, promotes mitochondrial fusion. As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression. Conclusions Placental mitochondrial fusion is enhanced in GDM, possibly as a compensatory response to maternal and fetal metabolic derangements. Alterations in placental insulin exposure and sphingolipid metabolism are among potential contributing factors. Overall, our results suggest that GDM has profound impacts on placental mitochondrial dynamics and metabolism, with plausible implications for the short-term and long-term health of the offspring. |
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Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis?GDMmitochondriaplacentaIntroduction Gestational diabetes mellitus (GDM), a common pregnancy disorder, increases the risk of fetal overgrowth and later metabolic morbidity in the offspring. The placenta likely mediates these sequelae, but the exact mechanisms remain elusive. Mitochondrial dynamics refers to the joining and division of these organelles, in attempts to maintain cellular homeostasis in stress conditions or alterations in oxygen and fuel availability. These remodeling processes are critical to optimize mitochondrial function, and their disturbances characterize diabetes and obesity. Methods and results Herein we show that placental mitochondrial dynamics are tilted toward fusion in GDM, as evidenced by transmission electron microscopy and changes in the expression of key mechanochemical enzymes such as OPA1 and active phosphorylated DRP1. In vitro experiments using choriocarcinoma JEG-3 cells demonstrated that increased exposure to insulin, which typifies GDM, promotes mitochondrial fusion. As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression. Conclusions Placental mitochondrial fusion is enhanced in GDM, possibly as a compensatory response to maternal and fetal metabolic derangements. Alterations in placental insulin exposure and sphingolipid metabolism are among potential contributing factors. Overall, our results suggest that GDM has profound impacts on placental mitochondrial dynamics and metabolism, with plausible implications for the short-term and long-term health of the offspring.Lunenfeld-Tanenbaum Research InstituteDepartamento de Ginecologia e Obstetrícia Faculdade de Medicina de BotucatuDepartment of Obstetrics and Gynecology Helsinki University Central HospitalDepartment of Obstetrics and Gynecology University of TorontoDepartment of Physiology and Institute of Medical Sciences University of TorontoHospital for Sick Children SickKids Learning InstituteDepartamento de Ginecologia e Obstetrícia Faculdade de Medicina de BotucatuLunenfeld-Tanenbaum Research InstituteUniversidade Estadual Paulista (UNESP)Helsinki University Central HospitalUniversity of TorontoHospital for Sick Children SickKids Learning InstituteAbbade, Joelcio [UNESP]Klemetti, Miira MarjuskaFarrell, AbbyErmini, LeonardoGillmore, TaylorSallais, JulienTagliaferro, AndreaPost, MartinCaniggia, Isabella2022-04-29T08:28:35Z2022-04-29T08:28:35Z2020-03-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1136/bmjdrc-2019-000923BMJ Open Diabetes Research and Care, v. 8, n. 1, 2020.2052-4897http://hdl.handle.net/11449/22878010.1136/bmjdrc-2019-0009232-s2.0-85081533110Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBMJ Open Diabetes Research and Careinfo:eu-repo/semantics/openAccess2024-08-16T14:06:30Zoai:repositorio.unesp.br:11449/228780Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-16T14:06:30Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis? |
title |
Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis? |
spellingShingle |
Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis? Abbade, Joelcio [UNESP] GDM mitochondria placenta |
title_short |
Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis? |
title_full |
Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis? |
title_fullStr |
Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis? |
title_full_unstemmed |
Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis? |
title_sort |
Increased placental mitochondrial fusion in gestational diabetes mellitus: An adaptive mechanism to optimize feto-placental metabolic homeostasis? |
author |
Abbade, Joelcio [UNESP] |
author_facet |
Abbade, Joelcio [UNESP] Klemetti, Miira Marjuska Farrell, Abby Ermini, Leonardo Gillmore, Taylor Sallais, Julien Tagliaferro, Andrea Post, Martin Caniggia, Isabella |
author_role |
author |
author2 |
Klemetti, Miira Marjuska Farrell, Abby Ermini, Leonardo Gillmore, Taylor Sallais, Julien Tagliaferro, Andrea Post, Martin Caniggia, Isabella |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Lunenfeld-Tanenbaum Research Institute Universidade Estadual Paulista (UNESP) Helsinki University Central Hospital University of Toronto Hospital for Sick Children SickKids Learning Institute |
dc.contributor.author.fl_str_mv |
Abbade, Joelcio [UNESP] Klemetti, Miira Marjuska Farrell, Abby Ermini, Leonardo Gillmore, Taylor Sallais, Julien Tagliaferro, Andrea Post, Martin Caniggia, Isabella |
dc.subject.por.fl_str_mv |
GDM mitochondria placenta |
topic |
GDM mitochondria placenta |
description |
Introduction Gestational diabetes mellitus (GDM), a common pregnancy disorder, increases the risk of fetal overgrowth and later metabolic morbidity in the offspring. The placenta likely mediates these sequelae, but the exact mechanisms remain elusive. Mitochondrial dynamics refers to the joining and division of these organelles, in attempts to maintain cellular homeostasis in stress conditions or alterations in oxygen and fuel availability. These remodeling processes are critical to optimize mitochondrial function, and their disturbances characterize diabetes and obesity. Methods and results Herein we show that placental mitochondrial dynamics are tilted toward fusion in GDM, as evidenced by transmission electron microscopy and changes in the expression of key mechanochemical enzymes such as OPA1 and active phosphorylated DRP1. In vitro experiments using choriocarcinoma JEG-3 cells demonstrated that increased exposure to insulin, which typifies GDM, promotes mitochondrial fusion. As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression. Conclusions Placental mitochondrial fusion is enhanced in GDM, possibly as a compensatory response to maternal and fetal metabolic derangements. Alterations in placental insulin exposure and sphingolipid metabolism are among potential contributing factors. Overall, our results suggest that GDM has profound impacts on placental mitochondrial dynamics and metabolism, with plausible implications for the short-term and long-term health of the offspring. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-03-05 2022-04-29T08:28:35Z 2022-04-29T08:28:35Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1136/bmjdrc-2019-000923 BMJ Open Diabetes Research and Care, v. 8, n. 1, 2020. 2052-4897 http://hdl.handle.net/11449/228780 10.1136/bmjdrc-2019-000923 2-s2.0-85081533110 |
url |
http://dx.doi.org/10.1136/bmjdrc-2019-000923 http://hdl.handle.net/11449/228780 |
identifier_str_mv |
BMJ Open Diabetes Research and Care, v. 8, n. 1, 2020. 2052-4897 10.1136/bmjdrc-2019-000923 2-s2.0-85081533110 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
BMJ Open Diabetes Research and Care |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128113497866240 |