title: Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies.
abstract: BACKGROUND
  Babies of obese women are often large at birth, which is associated with perinatal complications and metabolic syndrome later in life. The mechanisms linking maternal obesity to fetal overgrowth are largely unknown.
  
  
  OBJECTIVE
  We tested the hypothesis that placental insulin/IGF-I and mammalian target of rapamycin (mTOR) signaling is activated and amino acid transporter activity is increased in large babies of obese women.
  
  
  METHODS
  Pregnant women were recruited prospectively for collection of placental tissue at a university hospital and academic biomedical center.
  
  
  METHODS
  Twenty-three Swedish pregnant women with first trimester body mass index ranging from 18.5 to 44.9 kg/m(2) and with uncomplicated pregnancies participated in the study.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  We determined the phosphorylation of key signaling molecules (including Akt, IRS-1, S6K1, 4EBP-1, RPS6, and AMPK) in the placental insulin/IGF-I, AMPK, and mTOR signaling pathways. The activity and protein expression of the amino acid transporter systems A and L were measured in syncytiotrophoblast microvillous plasma membranes.
  
  
  RESULTS
  Birth weights (range, 3025-4235 g) were positively correlated to maternal body mass index (P < 0.05). The activity of placental insulin/IGF-I and mTOR signaling was positively correlated (P < 0.001), whereas AMPK phosphorylation was inversely (P < 0.05) correlated to birth weight. Microvillous plasma membrane system A, but not system L, activity and protein expression of the system A isoform SNAT2 were positively correlated to birth weight (P < 0.001).
  
  
  CONCLUSIONS
  Up-regulation of specific placental amino acid transporter isoforms may contribute to fetal overgrowth in maternal obesity. This effect may be mediated by activation of insulin/IGF-I and mTOR signaling pathways, which are positive regulators of placental amino acid transporters.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Jansson
authors.forename: Fredrick J
authors.initials: FJ
authors.lastname: Rosario
authors.forename: Francesca
authors.initials: F
authors.lastname: Gaccioli
authors.forename: Susanne
authors.initials: S
authors.lastname: Lager
authors.forename: Helen N
authors.initials: HN
authors.lastname: Jones
authors.forename: Sara
authors.initials: S
authors.lastname: Roos
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Powell
mesh_terms: D000328:Adult; D026905:Amino Acid Transport Systems / Q000819:agonists / Q000378:metabolism*; D001724:Birth Weight / Q000502:physiology; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005320:Fetal Macrosomia / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D026905:Amino Acid Transport Systems; D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases