PMID- 27357801
OWN - NLM
STAT- MEDLINE
DCOM- 20170630
LR  - 20220408
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 311
IP  - 3
DP  - 2016 Sep 1
TI  - Regulation of fetal liver growth in a model of diet restriction in the pregnant 
      rat.
PG  - R478-88
LID - 10.1152/ajpregu.00138.2016 [doi]
AB  - Limited nutrient availability is a cause of intrauterine growth restriction 
      (IUGR), a condition that has important implications for the well being of the 
      offspring. Using the established IUGR model of maternal fasting in the rat, we 
      investigated mechanisms that control gene expression and mRNA translation in 
      late-gestation fetal liver. Maternal fasting for 48 h during the last one-third 
      of gestation was associated with a 10-15% reduction in fetal body weight and a 
      disproportionate one-third reduction in total fetal liver protein. The fetal 
      liver transcriptome showed only subtle changes consistent with reduced cell 
      proliferation and enhanced differentiation in IUGR. Effects on the transcriptome 
      could not be attributed to specific transcription factors. We purified 
      translating polysomes to profile the population of mRNAs undergoing active 
      translation. Microarray analysis of the fetal liver translatome indicated a 
      global reduction of translation. The only targeted effect was enhanced 
      translation of mitochondrial ribosomal proteins in IUGR, consistent with enhanced 
      mitochondrial biogenesis. There was no evidence for attenuated signaling through 
      the mammalian target of rapamycin (mTOR). Western blot analysis showed no changes 
      in fetal liver mTOR signaling. However, eukaryotic initiation factor 2alpha (eIF2alpha) 
      phosphorylation was increased in livers from IUGR fetuses, consistent with a role 
      in global translation control. Our data indicate that IUGR-associated changes in 
      hepatic gene expression and mRNA translation likely involve a network of complex 
      regulatory mechanisms, some of which are novel and distinct from those that 
      mediate the response of the liver to nutrient restriction in the adult rat.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Boylan, Joan M
AU  - Boylan JM
AD  - Division of Pediatric Endocrinology, Rhode Island Hospital and Brown University, 
      Providence, Rhode Island;
FAU - Sanders, Jennifer A
AU  - Sanders JA
AD  - Division of Pediatric Endocrinology, Rhode Island Hospital and Brown University, 
      Providence, Rhode Island; Department of Pathology and Laboratory Medicine, Brown 
      University, Providence, Rhode Island; and.
FAU - Gruppuso, Philip A
AU  - Gruppuso PA
AD  - Division of Pediatric Endocrinology, Rhode Island Hospital and Brown University, 
      Providence, Rhode Island; Molecular Biology, Cell Biology, and Biochemistry, 
      Brown University, Providence, Rhode Island Philip_Gruppuso@brown.edu.
LA  - eng
GR  - R01 HD024455/HD/NICHD NIH HHS/United States
PT  - Journal Article
DEP - 20160629
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Multiprotein Complexes)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Caloric Restriction/adverse effects
MH  - *Fasting
MH  - Female
MH  - Fetal Growth Retardation/etiology/pathology/*physiopathology
MH  - Humans
MH  - Liver/*growth & development/*pathology
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/*metabolism
MH  - Pregnancy
MH  - Pregnancy, Animal
MH  - RNA, Messenger/metabolism
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transcriptome
PMC - PMC5142219
OTO - NOTNLM
OT  - fetus
OT  - liver
OT  - mTOR
OT  - protein synthesis
OT  - translation initiation
EDAT- 2016/07/01 06:00
MHDA- 2017/07/01 06:00
PMCR- 2017/09/01
CRDT- 2016/07/01 06:00
PHST- 2016/04/06 00:00 [received]
PHST- 2016/06/23 00:00 [accepted]
PHST- 2016/07/01 06:00 [entrez]
PHST- 2016/07/01 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2017/09/01 00:00 [pmc-release]
AID - ajpregu.00138.2016 [pii]
AID - R-00138-2016 [pii]
AID - 10.1152/ajpregu.00138.2016 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2016 Sep 1;311(3):R478-88. doi: 
      10.1152/ajpregu.00138.2016. Epub 2016 Jun 29.