Peroxisome proliferator-activated receptor-gamma and retinoid X receptor signaling regulate fatty acid uptake by primary human placental trophoblasts.
BACKGROUND
Transplacental transfer of fatty acids from the maternal to the fetal circulation is essential for fetal development. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates fatty acid transport and storage in adipocytes and other cell types.


OBJECTIVE
This study tested the hypothesis that PPARgamma and its heterodimeric nuclear receptor partner, retinoid X receptor (RXR), regulate fatty acid uptake by human trophoblasts.


METHODS
Prospective basic laboratory in vitro research was conducted using primary term human trophoblasts.


METHODS
The study was performed in the perinatal biology laboratory of an academic medical center.


METHODS
Study materials were obtained from healthy pregnant women at a gestational age of 37-41 wk.


METHODS
There were no interventions.


METHODS
Fat uptake and accumulation in human placental trophoblasts were measured.


RESULTS
We initially demonstrated that activation of PPARgamma and/or RXR with selective agonists increased the accumulation of neutral lipids in trophoblasts as well as uptake of free fatty acids. Furthermore, activation of PPARgamma and RXR enhanced the expression of the fat droplet-associated protein adipophilin along with fatty acid transport protein (FATP)4, whereas expression of FATP2 was decreased by activation of RXR. Finally, we found that inhibition of p38 MAPK, which diminishes the activity of PPARgamma in trophoblasts, inhibited fatty acid uptake and blocked the PPARgamma- and RXR-dependent increases in adipophilin and FATP4 expression, yet stimulated the expression of FATP1, FATP2, and FATP3.


CONCLUSIONS
These data support a role for PPARgamma and RXR in regulation of fatty acid transport and storage in human placental trophoblasts.
Schaiff
W Timothy
WT
Washington University School of Medicine, Department of Obstetrics and Gynecology, Campus Box 8064, 4566 Scott Avenue, St. Louis, Missouri 63110, USA.
Bildirici
Ibrahim
I
Cheong
Monica
M
Chern
Peggy L
PL
Nelson
D Michael
DM
Sadovsky
Yoel
Y
D002478:Cells, Cultured; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology*; D000070780:Perilipin-2; D047488:Retinoid X Receptors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C000602982:PLIN2 protein, human; D047495:PPAR gamma; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse; D047488:Retinoid X Receptors; C493568:SLC27A1 protein, human; C493571:SLC27A4 protein, human; C493572:Slc27a4 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases