Activation of phospholipase A2 is associated with generation of placental lipid signals and fetal obesity

Ali Varastehpour, Tatjana Radaelli, Judi Minium, Henar Ortega, Emilio Herrera, Patrick Catalano, Sylvie Hauguel-de Mouzon

Research output: Contribution to journalArticle

Abstract

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-α and leptin content was increased 3-fold in placenta of obese neonates. TNF-α 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-α and leptin stimulation represents a key mechanism to favor excess fetal fat accretion.

Original languageEnglish
Pages (from-to)248-255
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number1
DOIs
Publication statusPublished - Jan 2006

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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