title: Diet-induced obesity in mice reduces placental efficiency and inhibits placental mTOR signaling.
abstract: As in humans, obesity during pregnancy in mice results in elevated maternal insulin levels and metabolic programming of offspring. mTOR signaling regulates amino acid transport and may function as a placental nutrient sensor. Because obesity is a condition with increased nutrient availability, we hypothesized that diet-induced obesity activates placental mTOR signaling. To test this hypothesis, female C57BL/6J mice were fed an obesogenic diet or standard chow prior to and throughout pregnancy. Fetuses and placentas were collected at gestational day 18. Using Western blot analysis, placental mTOR activity was determined along with energy, inflammatory, and insulin signaling pathways (upstream modulators of mTOR). At gestational day 18, fetal and placental weights did not differ, however, in obese dams, the fetal/placental weight ratio was lower (P <0.01). In placentas from obese dams, mTOR signaling was inhibited, as determined by decreased Rheb and S6K1 expression, and lower rpS6 phosphorylation (P <0.05). In contrast, energy, inflammatory, and insulin signaling pathways were unaffected. Contrary to our hypothesis, diet-induced obesity in pregnant mice was associated with inhibition of placental mTOR signaling. However, this finding is consistent with the lower fetal/placental weight ratio, indicating reduced placental efficiency.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lager
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK.
authors.forename: Anne-Maj
authors.initials: AM
authors.lastname: Samulesson
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Taylor
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.affiliation: Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Powell
authors.affiliation: Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
keywords: Cell signaling; inflammation; insulin; pregnancy
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