PMID- 24006279
OWN - NLM
STAT- MEDLINE
DCOM- 20140527
LR  - 20211203
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Linking)
VI  - 89
IP  - 4
DP  - 2013 Oct
TI  - Maternal overweight induced by a diet with high content of saturated fat 
      activates placental mTOR and eIF2alpha signaling and increases fetal growth in 
      rats.
PG  - 96
LID - 10.1095/biolreprod.113.109702 [doi]
AB  - The mammalian target of rapamycin (mTOR) and the eukaryotic initiation factor 2 
      (eIF2) signaling pathways control protein synthesis in response to nutrient 
      availability. Moreover, mTOR is a positive regulator of placental nutrient 
      transport and is involved in the regulation of fetal growth. We hypothesized that 
      maternal overweight, induced by a diet with high saturated fat content, i) 
      up-regulates placental mTOR activity and nutrient transport, resulting in fetal 
      overgrowth; ii) inhibits phosphorylation of eIF2 at its alpha subunit 
      (eIF2alpha); and iii) leads to placental inflammation. Albino Wistar female rats 
      were fed a control or high-saturated-fat (HF) diet for 7 wk before mating and 
      during pregnancy. At gestational day 21, the HF diet significantly increased 
      maternal and fetal triglyceride, leptin, and insulin (but not glucose) levels and 
      maternal and fetal weights, and placental weights trended to increase. 
      Phosphorylated 4EBP1 (T37/46 and S65) was significantly higher, and 
      phosphorylated rpS6 (S235/236) tended to increase, in the placentas of dams fed 
      an HF diet, indicating an activation of mTOR complex 1 (mTORC1). Phosphorylation 
      of AMPK and eIF2alpha was reduced in the HF diet group compared to the control. 
      The expression and activity of placental nutrient transporters and lipoprotein 
      lipase (LPL), as well as the activation of inflammatory pathways, were not 
      altered by the maternal diet. We conclude that maternal overweight induced by an 
      HF diet stimulates mTORC1 activity and decreases eIF2alpha phosphorylation in rat 
      placentas. We speculate that these changes may up-regulate protein synthesis and 
      contribute to placental and fetal overgrowth.
FAU - Gaccioli, Francesca
AU  - Gaccioli F
AD  - Center for Pregnancy and Newborn Research, University of Texas Health Science 
      Center, San Antonio, Texas.
FAU - White, Veronica
AU  - White V
FAU - Capobianco, Evangelina
AU  - Capobianco E
FAU - Powell, Theresa L
AU  - Powell TL
FAU - Jawerbaum, Alicia
AU  - Jawerbaum A
FAU - Jansson, Thomas
AU  - Jansson T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131024
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Protein Subunits)
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  - Diet, High-Fat/adverse effects
MH  - Eukaryotic Initiation Factor-2/*metabolism
MH  - Female
MH  - Fetal Blood/metabolism
MH  - Fetal Macrosomia/blood/*etiology/immunology
MH  - Inflammation Mediators/blood/metabolism
MH  - *Maternal Nutritional Physiological Phenomena
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/*metabolism
MH  - Organ Size
MH  - Overweight/etiology/immunology/metabolism/*physiopathology
MH  - Phosphorylation
MH  - Placenta/immunology/*metabolism/pathology
MH  - Pregnancy
MH  - Pregnancy Complications/etiology/immunology/metabolism/*physiopathology
MH  - Protein Processing, Post-Translational
MH  - Protein Subunits/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - fetal overgrowth
OT  - maternal obesity
OT  - placental inflammation
OT  - placental transport
OT  - pregnancy
EDAT- 2013/09/06 06:00
MHDA- 2014/05/28 06:00
CRDT- 2013/09/06 06:00
PHST- 2013/09/06 06:00 [entrez]
PHST- 2013/09/06 06:00 [pubmed]
PHST- 2014/05/28 06:00 [medline]
AID - biolreprod.113.109702 [pii]
AID - 10.1095/biolreprod.113.109702 [doi]
PST - epublish
SO  - Biol Reprod. 2013 Oct 24;89(4):96. doi: 10.1095/biolreprod.113.109702. Print 2013 
      Oct.