The lipid droplet-associated protein adipophilin is expressed in human trophoblasts and is regulated by peroxisomal proliferator-activated receptor-gamma/retinoid X receptor.
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-gamma (PPARgamma) 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 PPARgamma. 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 PPARgamma 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 PPARgamma. Lastly, we demonstrated that ligand-activated PPARgamma 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 PPARgamma/RXR. Enhanced adipophilin expression may contribute to fatty acid uptake by the placenta.
Bildirici
Ibrahim
I
Departments of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Roh
Cheong-Rae
CR
Schaiff
W Timothy
WT
Lewkowski
Beth M
BM
Nelson
D Michael
DM
Sadovsky
Yoel
Y
D000924:Anticholesteremic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002839:Chromans / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins; D009930:Organic Chemicals; D009994:Osmolar Concentration; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D000070780:Perilipin-2; D010920:Placenta / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D047488:Retinoid X Receptors; D045162:Thiazolidinediones / Q000008:administration & dosage; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D000077288:Troglitazone; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000924:Anticholesteremic Agents; D002839:Chromans; C423914:LG 268; D008024:Ligands; D008565:Membrane Proteins; D009930:Organic Chemicals; C000602982:PLIN2 protein, human; D010455:Peptides; D000070780:Perilipin-2; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone