Maternal High-Fat Diet Disturbs Uteroplacental Hemodynamics and Increases the Frequency of Stillbirth in a Nonhuman Primate Model of Excess Nutrition
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Prepregnancy maternal obesity confers an increased risk of stillbirth, but the mechanisms are unknown. Maternal obesity is associated with placental inflammation. We considered that maternal diet may predispose to the increased risk of placental inflammation and stillbirth. We hypothesized that a chronic high-fat diet (HFD) is associated with abnormal uteroplacental circulation and placental inflammation. Here we used a nonhuman primate model to determine the effect of chronic HFD on the uterine and placental hemodynamics, placental histology, and inflammation in a prospective, observational study of 24 Japanese macaques. Overall, there was a statistically significant (38-56%) reduction in uterine volume blood flow from HFD animals, whether they were lean or obese. Consumption of a HFD, independent of obesity, increased placental inflammatory cytokines and the expression of Toll-like receptor 4. We show that HFD consumption by obese mothers with hyperinsulinemia also reduced volume blood flow on the fetal side of the placenta and significantly increased the frequency of both placental infarctions and stillbirth. These results suggest that a HFD, independent of obesity, decreases uterine volume blood flow. Maternal obesity and insulin resistance further exacerbates the placental dysfunction and results in an increased frequency of stillbirth.
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In non-human primates, feeding a high fat diet increases placental infarction and reduces utero-placental blood flow, more pronounced in mothers that become obese than in those who remained lean on the diet.
“In non-human primates, there are increases in placental infarction and reductions in utero-placental blood flow in response to feeding a high fat diet, which are more pronounced in mothers that become obese than in those who remained lean on the diet (200).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [200]
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- Authors
- Frias, A. E., Morgan, T. K., Evans, A. E., Rasanen, J., Oh, K. Y., Thornburg, K. L., & Grove, K. L.
- Affiliations
- Oregon National Primate Research Center (US)
- Oregon Health & Science University (US)
- Corresponding author
- Frias, Antonio E.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2011-03-29
- Volume
- 152
- Issue
- 6
- Pages
- 2456-2464
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3100625
- OpenAlex
- W1964355822
- Cited by
- 268
- References
- 44
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 9 · 2023: 9 · 2022: 16 · 2021: 12 · 2020: 19 · 2019: 16 · 2018: 26 · 2017: 16 · 2016: 24 · 2015: 35 · 2014: 19 · 2013: 22 · 2012: 17
- FWCI
- 26.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK090964, R01DK079194, R24 DK0909640-01, P30DK020593)
- National Center for Research Resources (P51RR000163, K01RR000163)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD034430, K12HD001243, K12HD043488)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Keywords
- maternal high-fat diet, stillbirth, uteroplacental hemodynamics, placental inflammation, maternal obesity, Japanese macaque, placental infarction, hyperinsulinemia, insulin resistance, TLR4, uterine blood flow
- MeSH terms
- Animals, Dietary Fats, Disease Models, Animal, Female, Hemodynamics, Humans, Macaca, Obesity, Placenta, Pregnancy, Pregnancy Complications, Regional Blood Flow, Uterus, Cytokines, Prenatal Nutritional Physiological Phenomena, Stillbirth
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