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

Departments of Obstetrics and Gynecology (I.B., C.-R.R., W.T.S., B.M.L., D.M.N., Y.S.) and Cell Biology and Physiology (I.B., C.-R.R., W.T.S., Y.S.), Washington University School of Medicine, St. Louis, Missouri 63110

Address all correspondence and requests for reprints to: Yoel Sadovsky, M.D., Washington University School of Medicine, Department of Obstetrics and Gynecology, Campus Box 8064, 4566 Scott Avenue, St. Louis, Missouri 63110. E-mail: sadovskyy{at}msnotes.wustl.edu.

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- (PPAR) 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 PPAR. 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 PPAR 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 PPAR. Lastly, we demonstrated that ligand-activated PPAR 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 PPAR/RXR. Enhanced adipophilin expression may contribute to fatty acid uptake by the placenta.

This work was supported by TUBITAK 1528-3208 (to I.B.), National Institutes of Health-Building Interdisciplinary Research Careers in Women’s Health (to W.T.S., a part of K12 HD 01459), NIH HD-29190 (to D.M.N.) and NIH ES-11597 (to Y.S.).

This study was presented, in part, at the 50th Annual Meeting of the Society for Gynecologic Investigation, Washington, D.C., March 2003.

Abbreviations: ADRP, Adipose differentiation-related protein; Ct, threshold cycle; Ct, Ct values; PPAR, peroxisome proliferator-activated receptor-; RXR, retinoid X receptor.

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