The Lipid Droplet-Associated Protein Adipophilin Is Expressed in Human Trophoblasts and Is Regulated by Peroxisomal Proliferator-Activated Receptor-γ/Retinoid X Receptor

Ibrahim Bildirici, Cheong Rae Roh, W. Timothy Schaiff, Beth M. Lewkowski, D. Michael Nelson, Yoel Sadovsky

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Uptake and transplacental transfer of fatty acids is essential for fetal development. Human adipophilin and its murine ortholog adipocyte differentiation-related protein are lipid droplet-associated proteins that are implicated in cellular fatty acid uptake in adipocytes. The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) stimulates lipid uptake by adipocytes and enhances differentiation of placental trophoblasts. We therefore hypothesized that adipophilin is expressed in human trophoblasts and that its expression is regulated by PPARγ. We initially determined that adipophilin is expressed in human villous trophoblasts and that adipophilin expression is enhanced during differentiation of cultured primary term human trophoblasts. We also found that exposure of cultured human trophoblasts to the PPARγ ligand troglitazone resulted in a concentration-dependent increase in adipophilin expression. We observed a similar increase with LG268, a ligand for retinoid X receptor (RXR), the heterodimeric partner of PPARγ. Lastly, we demonstrated that ligand-activated PPARγ and RXR stimulated the transcriptional activity of adipophilin promoter in CV-1 cells and in the placental JEG3 cell line. We conclude that the expression of adipophilin is enhanced during trophoblast differentiation and is up-regulated by ligand-activated PPARγ/ RXR. Enhanced adipophilin expression may contribute to fatty acid uptake by the placenta.

Original languageEnglish
Pages (from-to)6056-6062
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number12
DOIs
StatePublished - Dec 1 2003

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