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Activation of Placental mTOR Signaling and Amino Acid Transporters in Obese Women Giving Birth to Large Babies
Open accessAbstract
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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“Indeed, a linear relationship between placental mTOR activity and birth weight has been found across a wide range of maternal body mass index (279).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [279]
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“Thus, activity of system A, but not system L, transporters in the apical membrane of the syncytiotrophoblast correlates positively with birth weight, and may contribute to fetal overgrowth in cases of maternal obesity (279).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [279]
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“By contrast, increased placental mTOR signaling is associated with large for gestational age babies delivered by obese women (279).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [279]
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“By contrast, in obese women delivering larger infants, placental GLUT1 expression and System A activity are higher in the basal and microvillous membranes, respectively, than seen in women with a lean BMI (1,279).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [279]
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Metadata
- 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
- 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
- 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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