title: Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2alpha signaling and increases fetal growth in rats.
abstract: The mammalian target of rapamycin (mTOR) and the eukaryotic initiation factor 2 (eIF2) signaling pathways control protein synthesis in response to nutrient availability. Moreover, mTOR is a positive regulator of placental nutrient transport and is involved in the regulation of fetal growth. We hypothesized that maternal overweight, induced by a diet with high saturated fat content, i) up-regulates placental mTOR activity and nutrient transport, resulting in fetal overgrowth; ii) inhibits phosphorylation of eIF2 at its alpha subunit (eIF2alpha); and iii) leads to placental inflammation. Albino Wistar female rats were fed a control or high-saturated-fat (HF) diet for 7 wk before mating and during pregnancy. At gestational day 21, the HF diet significantly increased maternal and fetal triglyceride, leptin, and insulin (but not glucose) levels and maternal and fetal weights, and placental weights trended to increase. Phosphorylated 4EBP1 (T37/46 and S65) was significantly higher, and phosphorylated rpS6 (S235/236) tended to increase, in the placentas of dams fed an HF diet, indicating an activation of mTOR complex 1 (mTORC1). Phosphorylation of AMPK and eIF2alpha was reduced in the HF diet group compared to the control. The expression and activity of placental nutrient transporters and lipoprotein lipase (LPL), as well as the activation of inflammatory pathways, were not altered by the maternal diet. We conclude that maternal overweight induced by an HF diet stimulates mTORC1 activity and decreases eIF2alpha phosphorylation in rat placentas. We speculate that these changes may up-regulate protein synthesis and contribute to placental and fetal overgrowth.
authors.affiliation: Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gaccioli
authors.forename: Veronica
authors.initials: V
authors.lastname: White
authors.forename: Evangelina
authors.initials: E
authors.lastname: Capobianco
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Powell
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005320:Fetal Macrosomia / Q000097:blood / Q000209:etiology* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D009929:Organ Size; D050177:Overweight / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D010920:Placenta / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D018836:Inflammation Mediators; D046912:Multiprotein Complexes; D021122:Protein Subunits; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: fetal overgrowth; maternal obesity; placental inflammation; placental transport; pregnancy