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Cited by 176Birth, Development, and HealthPregnancy and preeclampsia studiesGrowth Hormone and Insulin-like Growth Factors

Maternal Protein Restriction in the Rat Inhibits Placental Insulin, mTOR, and STAT3 Signaling and Down-Regulates Placental Amino Acid Transporters

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Rosario, Fredrick J., Jansson, Nina, Kanai, Yoshikatsu, Prasad, Puttur D., Powell, Theresa L., Jansson, Thomas·2011·Endocrinology
DOI 10.1210/en.2010-1153PMC PMC3858644
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Abstract

The mechanisms underlying reduced fetal growth in response to maternal protein restriction are not well established. Maternal levels of insulin, IGF-I, and leptin are decreased in rats fed a low protein (LP) diet. Because these hormones stimulate placental amino acid transporters in vitro, we hypothesized that maternal protein restriction inhibits placental leptin, insulin/IGF-I, and mammalian target of rapamycin signaling and down-regulates the expression and activity of placental amino acid transporters. Pregnant rats were fed either an isocaloric low protein (LP, 4% protein) or control diet (18% protein) and studied at gestational day (GD)15, GD19, or GD21 (term 23). At GD19 and GD21, placental expression of phosphorylated eukaryotic initiation factor 4E binding protein 1 (Thr-36/46 or Thr-70) and phosphorylated S6 ribosomal protein (Ser-235/236) was decreased in the LP group. In addition, placental expression of phosphorylated S6 kinase 1 (Thr-389), phosphorylated Akt (Thr-308), and phosphorylated signal transducer and activator of transcription 3 (Tyr-705) was reduced at GD21. In microvillous plasma membranes (MVM) isolated from placentas of LP animals, protein expression of the sodium-coupled neutral amino acid transporter (SNAT)2 and the large neutral amino acid transporters 1 and 2 was reduced at GD19 and GD21. MVM SNAT1 protein expression was reduced at GD21 in LP rats. SNAT4 and 4F2 heavy chain expression in MVM was unaltered. System A and L amino acid transporter activity was decreased in MVM from LP animals at GD19 and GD21. In conclusion, maternal protein restriction inhibits placental insulin, mammalian target of rapamycin signaling, and signal transducer and activator of transcription 3 signaling, which is associated with a down-regulation of placental amino acid transporters. We speculate that maternal endocrine and metabolic control of placental nutrient transport reduces fetal growth in response to protein restriction.

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  • Nutrient restriction leads to reduced mTOR activity, along with reduced insulin and AKT signaling, in rats fed a low protein diet and mice fed 80% of the control ad libitum diet.

    “Evidence from downstream signaling indicates that nutrient restriction leads to reduced mTOR activity, along with reduced insulin and AKT signaling, in rats fed a low protein diet (470), and mice fed 80% of the control ad libitum diet (495), as might be expected.”

    From Placental Origins of Chronic Disease (2016) · cites this paper as [470]

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Authors
Rosario, F. J., Jansson, N., Kanai, Y., Prasad, P. D., Powell, T. L., & Jansson, T.
Affiliations
  • The University of Texas at San Antonio Health Science Center (US)
  • University of Gothenburg (SE)
  • The University of Osaka (JP)
  • Augusta University (US)
Corresponding author
Rosario, Fredrick J.
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2011-03-01
Volume
152
Issue
3
Pages
1119-1129
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2010-1153
PMC
PMC3858644
OpenAlex
W2077283526
Cited by
176
References
71
Citations by year
2026: 6 · 2025: 8 · 2024: 10 · 2023: 7 · 2022: 9 · 2021: 15 · 2020: 24 · 2019: 6 · 2018: 12 · 2017: 17 · 2016: 11 · 2015: 13 · 2014: 7 · 2013: 12 · 2012: 15
FWCI
11.19
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Endocrinology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089989)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
maternal protein restriction, low-protein diet, placenta, fetal growth restriction, insulin signaling, insulin-like growth factor I, leptin, mTOR signaling, STAT3 signaling, eIF4E phosphorylation, ribosomal protein S6, Akt, SNAT2, SNAT1, amino acid transporters, placental nutrient transport
MeSH terms
Animals, Carrier Proteins, Diet, Dietary Proteins, Female, Gene Expression Regulation, Insulin, Phosphoproteins, Phosphorylation, Placenta, Placentation, Pregnancy, Signal Transduction, Weight Gain, Ribosomal Protein S6 Kinases, Fetal Weight, Amino Acid Transport Systems, Maternal Nutritional Physiological Phenomena, Intracellular Signaling Peptides and Proteins, STAT3 Transcription Factor, Proto-Oncogene Proteins c-akt, Rats, TOR Serine-Threonine Kinases

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