PMID- 30835509
OWN - NLM
STAT- MEDLINE
DCOM- 20200102
LR  - 20211204
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 316
IP  - 5
DP  - 2019 May 1
TI  - Apelin is a novel regulator of human trophoblast amino acid transport.
PG  - E810-E816
LID - 10.1152/ajpendo.00012.2019 [doi]
AB  - Apelin is an insulin-sensitizing hormone increased in abundance with obesity. 
      Apelin and its receptor, APJ, are expressed in the human placenta, but whether 
      apelin regulates placental function in normal body mass index (BMI) and obese 
      pregnant women remains unknown. We hypothesized that apelin stimulates amino acid 
      transport in cultured primary human trophoblast (PHT) cells and that maternal 
      circulating apelin levels are elevated in obese pregnant women delivering large 
      babies. Treating PHT cells with physiological concentrations of the 
      pyroglutamated form [Pyr(1)]apelin-13 (0.1-10.0 ng/ml) for 24 h dose-dependently 
      increased System A amino acid transport (P < 0.05) but did not affect System L 
      transport activity. Mechanistic target of rapamycin (mTOR), extracellular 
      signal-regulated kinase-1/2 (ERK1/2), and AMP-activated protein kinase-alpha (AMPKalpha) 
      signaling were unaffected by apelin (P > 0.05). Plasma apelin was not different 
      in obese women (BMI 35.8 +/- 0.7, n = 21) with large babies compared with 
      normal-BMI women (23.1 +/- 0.5, n = 16) delivering normal birth weight infants. 
      Apelin was highly expressed in placental villous tissue (20-fold higher vs. 
      adipose), and APJ was present in syncytiotrophoblast microvillous membrane, but 
      neither differed in abundance between normal-BMI and obese women. Phosphorylation 
      (Thr(172)) of placental AMPKalpha strongly correlated with microvillous membrane APJ 
      expression (P < 0.01, R = 0.63) but negatively correlated with placental apelin 
      abundance (P < 0.01, R = -0.62). Neither placental APJ nor apelin abundance 
      correlated with maternal BMI, plasma insulin, birth weight, or mTOR or ERK1/2 
      signaling (P > 0.05). Hence, apelin stimulates trophoblast amino acid uptake, 
      establishing a novel mechanism regulating placental function. We found no 
      evidence that apelin constitutes an endocrine link between maternal obesity and 
      fetal overgrowth.
FAU - Vaughan, O R
AU  - Vaughan OR
AUID- ORCID: 0000-0001-7537-3264
AD  - Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical 
      Campus , Aurora, Colorado.
FAU - Powell, T L
AU  - Powell TL
AD  - Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical 
      Campus , Aurora, Colorado.
AD  - Department of Pediatrics, University of Colorado Anschutz Medical Campus , 
      Aurora, Colorado.
FAU - Jansson, T
AU  - Jansson T
AD  - Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical 
      Campus , Aurora, Colorado.
LA  - eng
GR  - UL1 TR002535/TR/NCATS NIH HHS/United States
GR  - R01 HD068370/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190305
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (APLN protein, human)
RN  - 0 (APLNR protein, human)
RN  - 0 (Amino Acid Transport System A)
RN  - 0 (Amino Acid Transport System L)
RN  - 0 (Amino Acid Transport Systems)
RN  - 0 (Apelin)
RN  - 0 (Apelin Receptors)
RN  - 0 (Insulin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Adult
MH  - Amino Acid Transport System A/metabolism
MH  - Amino Acid Transport System L/metabolism
MH  - Amino Acid Transport Systems/*metabolism
MH  - Apelin/*metabolism
MH  - Apelin Receptors/metabolism
MH  - Birth Weight
MH  - Case-Control Studies
MH  - Female
MH  - Fetal Macrosomia/metabolism
MH  - Humans
MH  - Infant, Newborn
MH  - Insulin/metabolism
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Microvilli/metabolism
MH  - Obesity, Maternal/*metabolism
MH  - Placenta/metabolism
MH  - Pregnancy
MH  - Primary Cell Culture
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Trophoblasts/*metabolism
PMC - PMC6580166
OTO - NOTNLM
OT  - System A
OT  - adipokine
OT  - fetus
OT  - obesity
OT  - placenta
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2019/03/06 06:00
MHDA- 2020/01/03 06:00
PMCR- 2020/05/01
CRDT- 2019/03/06 06:00
PHST- 2019/03/06 06:00 [pubmed]
PHST- 2020/01/03 06:00 [medline]
PHST- 2019/03/06 06:00 [entrez]
PHST- 2020/05/01 00:00 [pmc-release]
AID - E-00012-2019 [pii]
AID - 10.1152/ajpendo.00012.2019 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2019 May 1;316(5):E810-E816. doi: 
      10.1152/ajpendo.00012.2019. Epub 2019 Mar 5.