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Activation of Phospholipase A2 Is Associated with Generation of Placental Lipid Signals and Fetal Obesity

Department of Reproductive Biology (A.V., T.R., J.M., P.C., S.H.-d.M.), Shwartz Center for Nutrition and Metabolism, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio 44109; and Universidad San Pablo-CEU (H.O., E.H.), E-28668 Madrid, Spain

Address all correspondence and requests for reprints to: Sylvie Hauguel-de Mouzon, Ph.D., Department of Reproductive Biology, Shwartz Center for Nutrition and Metabolism, MetroHealth Medical Center, Case Western Reserve University, 2550 MetroHealth Drive, Cleveland, Ohio 44109. E-mail: shdemouzon{at}metrohealth.org.

Context: Obesity and diabetes during pregnancy are associated with increased insulin resistance and higher neonatal adiposity. In turn, insulin resistance triggers inflammatory pathways with accumulation of placental cytokines.

Objective: To determine placental signals that translate into development of excess adipose tissue, we investigated the role of phospholipases A2 (PLA2) as targets of inflammatory mediators.

Setting: The study was conducted at Case Western Reserve University, Department of Reproductive Biology.

Subjects: Volunteers gave informed written consent in accordance with the Institutional Review Board guidelines. Placenta and cord blood samples were obtained at the time of elective cesarean section in 15 term pregnancies.

Intervention: Neonatal anthropometric measurements were performed within 48 h of delivery. Placentas were grouped based on neonatal percentage body fat as obese (body fat 16%) and lean control (body fat 8%).

Main Outcome Measures: The primary outcomes were placenta PLA2 expression and fatty acid concentration.

Results: Expression of PLA2G2A and PLA2G5, the main placenta phospholipases, was greater (P < 0.05) in placenta of obese compared with control neonates and was associated with increased 20:3 and 20:5 omega-3 polyunsaturated fatty acids. TNF- and leptin content was increased 3-fold in placenta of obese neonates. TNF- and leptin both induced a time-dependent activation of PLA2G2 and PLA2G5 in placental cells.

Conclusion: Accumulation of omega-3 fatty acids through secretory PLA2 activation is associated with high neonatal adiposity. We propose that the generation of placental lipid mediators through TNF- and leptin stimulation represents a key mechanism to favor excess fetal fat accretion.

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