PMID- 38223199
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240501
IS  - 2573-9832 (Electronic)
IS  - 2573-9832 (Linking)
VI  - 6
IP  - 1
DP  - 2024 Jan
TI  - Oleic acid stimulation of amino acid uptake in primary human trophoblast cells is 
      mediated by phosphatidic acid and mTOR signaling.
PG  - 1-11
LID - 10.1096/fba.2023-00113 [doi]
AB  - Normal fetal development is critically dependent on optimal nutrient supply by 
      the placenta, and placental amino acid transport has been demonstrated to be 
      positively associated with fetal growth. Mechanistic target of rapamycin (mTOR) 
      is a positive regulator of placental amino acid transporters, such as System A. 
      Oleic acid (OA) has been previously shown to have a stimulatory role on placental 
      mTOR signaling and System A amino acid uptake in primary human trophoblast (PHT) 
      cells. We investigated the mechanistic link between OA and System A activity in 
      PHT. We found that inhibition of mTOR complex 1 or 2, using small interfering RNA 
      to knock down raptor or rictor, prevented OA-stimulated System A amino acid 
      transport indicating the interaction of OA with mTOR. Phosphatidic acid (PA) is a 
      key intermediary for phospholipid biosynthesis and a known regulator of the mTOR 
      pathway; however, phospholipid biosynthetic pathways have not been extensively 
      studied in placenta. We identified placental isoforms of acyl transferase enzymes 
      involved in de novo phospholipid synthesis. Silencing of 
      1-acylglycerol-3-phosphate-O-acyltransferase-4, an enzyme in this pathway, 
      prevented OA mediated stimulation of mTOR and System A amino acid transport. 
      These data indicate that OA stimulates mTOR and amino acid transport in PHT cells 
      mediated through de novo synthesis of PA. We speculate that fatty acids in the 
      maternal circulation, such as OA, regulate placental functions critical for fetal 
      growth by interaction with mTOR and that late pregnancy hyperlipidemia may be 
      critical for increasing nutrient transfer to the fetus.
CI  - (c) 2023 The Authors. FASEB BioAdvances published by the Federation of American 
      Societies for Experimental Biology.
FAU - Silva, Elena
AU  - Silva E
AUID- ORCID: 0000-0002-1579-7484
AD  - Department of Obstetrics & Gynecology University of Colorado Anschutz Medical 
      Campus Aurora Colorado USA.
FAU - Ferchaud-Roucher, Veronique
AU  - Ferchaud-Roucher V
AUID- ORCID: 0000-0001-6809-1488
AD  - University of Nantes-INRAE UMR 1280 PhAN, CHU Nantes France.
FAU - Kramer, Anita
AU  - Kramer A
AD  - Department of Obstetrics & Gynecology University of Colorado Anschutz Medical 
      Campus Aurora Colorado USA.
FAU - Madi, Lana
AU  - Madi L
AD  - Department of Obstetrics & Gynecology University of Colorado Anschutz Medical 
      Campus Aurora Colorado USA.
FAU - Pantham, Priyadarshini
AU  - Pantham P
AD  - Ob/Gyn & Reproductive Sciences University of California, San Diego La Jolla 
      California USA.
FAU - Chassen, Stephanie
AU  - Chassen S
AUID- ORCID: 0000-0001-6004-6463
AD  - Department of Pediatrics, Section of Neonatology University of Colorado, Anschutz 
      Medical Campus Aurora Colorado USA.
FAU - Jansson, Thomas
AU  - Jansson T
AUID- ORCID: 0000-0002-8123-9480
AD  - Department of Obstetrics & Gynecology University of Colorado Anschutz Medical 
      Campus Aurora Colorado USA.
FAU - Powell, Theresa L
AU  - Powell TL
AUID- ORCID: 0000-0001-7410-1080
AD  - Department of Obstetrics & Gynecology University of Colorado Anschutz Medical 
      Campus Aurora Colorado USA.
AD  - Department of Pediatrics, Section of Neonatology University of Colorado, Anschutz 
      Medical Campus Aurora Colorado USA.
LA  - eng
GR  - R01 HD104644/HD/NICHD NIH HHS/United States
GR  - UL1 TR001082/TR/NCATS NIH HHS/United States
GR  - UM1 TR004399/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20231114
PL  - United States
TA  - FASEB Bioadv
JT  - FASEB bioAdvances
JID - 101733210
PMC - PMC10782470
OTO - NOTNLM
OT  - Kennedy pathway
OT  - fatty acids
OT  - human
OT  - maternal-fetal exchange
OT  - mechanistic target of rapamycin
OT  - phosphatidic acid
OT  - placenta
OT  - pregnancy
EDAT- 2024/01/15 06:43
MHDA- 2024/01/15 06:44
PMCR- 2023/11/14
CRDT- 2024/01/15 04:43
PHST- 2023/10/09 00:00 [received]
PHST- 2023/10/19 00:00 [revised]
PHST- 2023/10/30 00:00 [accepted]
PHST- 2024/01/15 06:44 [medline]
PHST- 2024/01/15 06:43 [pubmed]
PHST- 2024/01/15 04:43 [entrez]
PHST- 2023/11/14 00:00 [pmc-release]
AID - FBA21419 [pii]
AID - 10.1096/fba.2023-00113 [doi]
PST - epublish
SO  - FASEB Bioadv. 2023 Nov 14;6(1):1-11. doi: 10.1096/fba.2023-00113. eCollection 
      2024 Jan.