Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2alpha signaling and increases fetal growth in rats.

F GACCIOLI; V WHITE, ; E CAPOBIANCO; TL POWELL, T JANSSON ; A JAWERBAUM

BIOLOGY OF REPRODUCTION (ONLINE)

New York Academic Press

Año: 2013 p. 1 - 11

1529-7268

The mammalian target of rapamycin (mTOR) and theeukaryotic initiation factor 2 (eIF2) signaling pathways controlprotein synthesis in response to nutrient availability. Moreover,mTOR is a positive regulator of placental nutrient transport andis involved in the regulation of fetal growth. We hypothesizedthat maternal overweight, induced by a diet with high saturatedfat content, i) up-regulates placental mTOR activity and nutrienttransport, resulting in fetal overgrowth; ii) inhibits phosphorylationof eIF2 at its alpha subunit (eIF2alpha); and iii) leads toplacental inflammation. Albino Wistar female rats were fed acontrol or high-saturated-fat (HF) diet for 7 wk before matingand during pregnancy. At Gestational Day 21, the HF dietsignificantly increased maternal and fetal triglyceride, leptin,and insulin (but not glucose) levels and maternal and fetalweights, and placental weights trended to increase. Phosphorylated4EBP1 (T37/46 and S65) was significantly higher, andphosphorylated rpS6 (S235/236) tended to increase, in theplacentas of dams fed an HF diet, indicating an activation ofmTOR Complex 1 (mTORC1). Phosphorylation of AMPK andeIF2alpha was reduced in the HF diet group compared to thecontrol. The expression and activity of placental nutrienttransporters and lipoprotein lipase (LPL), as well as theactivation of inflammatory pathways, were not altered by thematernal diet. We conclude that maternal overweight inducedby an HF diet stimulates mTORC1 activity and decreaseseIF2alpha phosphorylation in rat placentas. We speculate thatthese changes may up-regulate protein synthesis and contributeto placental and fetal overgrowth.