Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters

Fredrick J. Rosario, Nina Jansson, Yoshikatsu Kanai, Puttur D. Prasad, Theresa L. Powell, Thomas Jansson

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1119-1129
Number of pages11
JournalEndocrinology
Volume152
Issue number3
DOIs
StatePublished - Mar 1 2011

Fingerprint

Amino Acid Transport Systems
Down-Regulation
Mothers
Insulin
Proteins
Cell Membrane
STAT3 Transcription Factor
Sirolimus
Fetal Development
Leptin
Insulin-Like Growth Factor I
Large Neutral Amino Acid-Transporter 1
CD98 Heavy Chain Antigens
Blood Proteins
Membrane Proteins
Neutral Amino Acid Transport Systems
Placental Hormones
Ribosomal Protein S6
Eukaryotic Initiation Factor-4E
Ribosomal Protein S6 Kinases

ASJC Scopus subject areas

  • Endocrinology

Cite this

Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. / Rosario, Fredrick J.; Jansson, Nina; Kanai, Yoshikatsu; Prasad, Puttur D.; Powell, Theresa L.; Jansson, Thomas.

In: Endocrinology, Vol. 152, No. 3, 01.03.2011, p. 1119-1129.

Research output: Contribution to journalArticle

Rosario, Fredrick J. ; Jansson, Nina ; Kanai, Yoshikatsu ; Prasad, Puttur D. ; Powell, Theresa L. ; Jansson, Thomas. / Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. In: Endocrinology. 2011 ; Vol. 152, No. 3. pp. 1119-1129.
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