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Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice

Objective  This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design  Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet...

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Autores principales: Grace, Matthew R., Dotters-Katz, Sarah K., Zhou, Chunxiao, Manuck, Tracy, Boggess, Kim, Bae-Jump, Victoria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Thieme Medical Publishers 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456331/
https://www.ncbi.nlm.nih.gov/pubmed/30972229
http://dx.doi.org/10.1055/s-0039-1683362
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author Grace, Matthew R.
Dotters-Katz, Sarah K.
Zhou, Chunxiao
Manuck, Tracy
Boggess, Kim
Bae-Jump, Victoria
author_facet Grace, Matthew R.
Dotters-Katz, Sarah K.
Zhou, Chunxiao
Manuck, Tracy
Boggess, Kim
Bae-Jump, Victoria
author_sort Grace, Matthew R.
collection PubMed
description Objective  This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design  Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression. Results  20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression ( p  < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated ( p  < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls ( p  = 0.001). Conclusion  Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy.
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spelling pubmed-64563312019-04-10 Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice Grace, Matthew R. Dotters-Katz, Sarah K. Zhou, Chunxiao Manuck, Tracy Boggess, Kim Bae-Jump, Victoria AJP Rep Objective  This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design  Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression. Results  20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression ( p  < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated ( p  < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls ( p  = 0.001). Conclusion  Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy. Thieme Medical Publishers 2019-04 2019-04-09 /pmc/articles/PMC6456331/ /pubmed/30972229 http://dx.doi.org/10.1055/s-0039-1683362 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.
spellingShingle Grace, Matthew R.
Dotters-Katz, Sarah K.
Zhou, Chunxiao
Manuck, Tracy
Boggess, Kim
Bae-Jump, Victoria
Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_full Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_fullStr Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_full_unstemmed Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_short Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_sort effect of a high-fat diet and metformin on placental mtor signaling in mice
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456331/
https://www.ncbi.nlm.nih.gov/pubmed/30972229
http://dx.doi.org/10.1055/s-0039-1683362
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