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

Matthew R. Grace; Sarah K. Dotters-Katz; Chunxiao Zhou; Tracy Manuck; Kim Boggess; Victoria Bae-Jump

doi:10.1055/s-0039-1683362

American Journal of Perinatology Reports, Table of Contents

CC BY-NC-ND 4.0 · AJP Rep 2019; 09(02): e138-e143
DOI: 10.1055/s-0039-1683362

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Matthew R. Grace

¹Tennessee Maternal Fetal Medicine and the University of Tennessee, Division of Obstetrics and Gynecology, Department of Clinical Medicine Education, Nashville, Tennessee

,

Sarah K. Dotters-Katz

²Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina

,

Chunxiao Zhou

³Division of Gynecologic Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

,

Tracy Manuck

⁴Division of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

⁵Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology and Carolina Institute for Environmental Health Solutions, University of North Carolina School of Medicine, Chapel Hill, North Carolina

,

Kim Boggess

⁴Division of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

,

Victoria Bae-Jump

³Division of Gynecologic Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

› Author Affiliations

Abstract

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.

Keywords

metformin - mTOR - mice - high-fat diet

Full Text

References

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