Cited by 305Pregnancy and preeclampsia studiesGestational Diabetes Research and ManagementBirth, Development, and Health

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Activation of Placental mTOR Signaling and Amino Acid Transporters in Obese Women Giving Birth to Large Babies

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Jansson, Nina, Rosario, Fredrick J., Gaccioli, Francesca, Lager, Susanne, Jones, Helen N., Roos, Sara, Jansson, Thomas, Powell, Theresa L.·2013·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2012-2667PMC PMC3537112

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Abstract

CONTEXT: 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. DESIGN AND SETTING: Pregnant women were recruited prospectively for collection of placental tissue at a university hospital and academic biomedical center. PATIENTS OR OTHER PARTICIPANTS: 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. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: 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.

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Authors: Jansson, N., Rosario, F. J., Gaccioli, F., Lager, S., Jones, H. N., Roos, S., Jansson, T., & Powell, T. L.
Affiliations: The University of Texas at San Antonio Health Science Center (US)
Cincinnati Children's Hospital Medical Center (US)
University of Gothenburg (SE)
Corresponding author: Powell, Theresa L.
ORCID: Rosario, Fredrick J.
Gaccioli, Francesca
Lager, Susanne
Jones, Helen N.
Roos, Sara
Jansson, Thomas
Powell, Theresa L.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2013-01
Volume: 98
Issue: 1
Pages: 105-113
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2012-2667
PMC: PMC3537112
OpenAlex: W1973061822
Cited by: 305
References: 43
Citations by year: 2026: 13 · 2025: 18 · 2024: 19 · 2023: 23 · 2022: 21 · 2021: 22 · 2020: 29 · 2019: 28 · 2018: 21 · 2017: 31 · 2016: 23 · 2015: 31 · 2014: 15 · 2013: 9
FWCI: 21.61
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Vetenskapsrådet (14555)
National Institutes of Health (5r01hd068370-11, HD68370)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089989, DK89989)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01-HD068370, HD68370)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords: maternal obesity, macrosomia, placenta, mTOR signaling, amino acid transporters, system A, SNAT2, system L, AMPK, syncytiotrophoblast, birth weight, S6K1, 4E-BP1, Akt, IRS-1
MeSH terms: Adult, Birth Weight, Female, Fetal Macrosomia, Humans, Infant, Newborn, Insulin-Like Growth Factor I, Obesity, Placenta, Pregnancy, Pregnancy Complications, Cohort Studies, Signal Transduction, Body Mass Index, Amino Acid Transport Systems, Young Adult, TOR Serine-Threonine Kinases

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Activation of Placental mTOR Signaling and Amino Acid Transporters in Obese Women Giving Birth to Large Babies

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