Article | Published:

Animal Models

Maternal high-fat diet reversal improves placental hemodynamics in a nonhuman primate model of diet-induced obesity

International Journal of Obesity (2018) | Download Citation

Abstract

Background

In a Japanese macaque model of diet-induced obesity, we have previously demonstrated that consumption of a high-fat, “Western-style” diet (WSD) is associated with placental dysfunction and adverse pregnancy outcomes, independent of an obese maternal phenotype. Specifically, we have reported decreased uterine placental blood flow and increased inflammation with maternal WSD consumption. We also previously investigated the use of a promising therapeutic intervention that mitigated the adverse placental effects of a WSD but had unexpected detrimental effects on fetal pancreatic development. Thus, the objective of the current study was to determine whether simple preconception diet reversal (REV) would improve placental function.

Methods

Female Japanese macaques were divided into three groups: REV animals (n = 5) were switched from a chronic WSD (36% fat) to a low fat, CON diet (14% fat) prior to conception and throughout pregnancy. The CON (n = 6) and WSD (n = 6) cohorts were maintained on their respective diets throughout pregnancy. Maternal body weight and composition were regularly assessed and advanced noninvasive imaging was performed at midgestation (gestational day 90, G90, or 0.5 of gestation, where full term is G175), and G129, 1 day prior to C-section delivery at G130 (0.75 of gestation). Imaging studies comprised Doppler ultrasound (US), contrast-enhanced US, and dynamic contrast-enhanced magnetic resonance imaging to assess uteroplacental hemodynamics and maternal-side placental perfusion.

Results

Dietary intervention resulted in significant maternal weight loss prior to pregnancy, and improved lean to fat mass ratio. By advanced imaging we demonstrated that a chronic WSD led to decreased blood flow velocity in the intervillous space, delayed blood flow transfer through the maternal spiral arteries, and reduced total placental blood flow compared to CON fed animals. Dietary reversal ameliorated these concerning derangements, restoring these hemodynamic parameters to CON levels.

Conclusions

Preconception dietary modification has beneficial effects on the maternal metabolic phenotype, and results in improved placental hemodynamics.

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Acknowledgments

The authors thank Diana Takahashi, Karalee Baquero, Jessica Walker, Peter Blundell, and Tyler Dean (Oregon National Primate Research Center) for technical assistance and guidance with the animal studies.

Funding

Supported by NIH #R21HD076265, and NIH #R24DK0909640. In addition, research reported in this publication was supported by the Office of the Director, National Institutes of Health of the National Institutes of Health under Award Number P51OD011092. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Affiliations

  1. Department of Obstetrics & Gynecology, Oregon Health & Science University, 3181 S W Sam Jackson Park Rd, Portland, OR, 97239, USA

    • Jennifer A. Salati
    • , Jamie O. Lo
    •  & Antonio E. Frias
  2. Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR, 97006, USA

    • Victoria H. J. Roberts
    • , Katherine S. Lewandowski
    •  & Antonio E. Frias
  3. Advanced Imaging Research Center, Oregon Health & Science University, 3181 S W Sam Jackson Park Rd, Portland, OR, 97239, USA

    • Matthias C. Schabel
    •  & Christopher D. Kroenke
  4. Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, UT, 84112, USA

    • Matthias C. Schabel
  5. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, 505 NW 185th Ave, Beaverton, OR, 97006, USA

    • Christopher D. Kroenke
  6. Knight Cardiovascular Institute, Oregon Health & Science University, 3303 S W Bond Ave., Portland, OR, 97239, USA

    • Jonathan R. Lindner
  7. Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR, 97006, USA

    • Jonathan R. Lindner
  8. Novo Nordisk Research Center, 530 Fairview Ave N #5000, Seattle, WA, 98109, USA

    • Kevin L. Grove

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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Victoria H. J. Roberts.

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DOI

https://doi.org/10.1038/s41366-018-0145-7