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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Thieme Medical Publishers
2019
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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. |
format | Online Article Text |
id | pubmed-6456331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Thieme Medical Publishers |
record_format | MEDLINE/PubMed |
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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