J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M500527-JLR200 on January 3, 2006

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Journal of Lipid Research, Vol. 47, 815-823, April 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Regulation of ADRP expression by long-chain polyunsaturated fatty acids in BeWo cells, a human placental choriocarcinoma cell line

Kari Anne Risan Tobin*,1, Nina Kittelsen Harsem{dagger}, Knut Tomas Dalen*, Anne Cathrine Staff{dagger}, Hilde Irene Nebb* and Asim K. Duttaroy*

* Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
{dagger} Department of Obstetrics and Gynecology, Ulleval University Hospital, Oslo, Norway

Published, JLR Papers in Press, January 3, 2006.

1 To whom correspondence should be addressed. e-mail: k.a.r.tobin{at}medisin.uio.no

Transplacental transfer of maternal fatty acids is critical for fetal growth and development. In the placenta, a preferential uptake of fatty acids toward long-chain polyunsaturated fatty acids (LCPUFAs) has been demonstrated. Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that has been ascribed a role in cellular fatty acid uptake and storage. However, its role in placenta is not known. We demonstrate that ADRP mRNA and protein are regulated by fatty acids in a human placental choriocarcinoma cell line (BeWo) and in primary human trophoblasts. LCPUFAs of the n-3 and n-6 series [arachidonic acid (20:4n-6), docosahexaenoic acid (22:6n-3), and eicosapentaenoic acid (20:5n-3)] were more efficient than shorter fatty acids at stimulating ADRP mRNA expression. The fatty acid-mediated increase in ADRP mRNA expression was not related to the differentiation state of the cells. Synthetic peroxisome proliferator-activated receptor and retinoic X receptor agonists increased ADRP mRNA level but had no effect on ADRP protein level in undifferentiated BeWo cells. Furthermore, we show that incubation of BeWo cells with LCPUFAs, but not synthetic agonists, increased the cellular content of radiolabeled oleic acid, coinciding with the increase in ADRP mRNA and protein level. These studies provide new information on the regulation of ADRP in placental trophoblasts and suggest that LCPUFA-dependent regulation of ADRP could be involved in the metabolism of lipids in the placenta.

Supplementary key words adipose differentiation-related protein • adipophilin • peroxisome proliferator-activated receptor • mRNA • gene regulation • tail-interacting protein of 47 kDa • trophoblasts

Abbreviations: AA, arachidonic acid; ADRP, adipose differentiation-related protein; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FCS, fetal calf serum; hCG, human chorionic gonadotropin; LCPUFA, long-chain polyunsaturated fatty acid; LD, lipid droplet; {alpha}-LN, {alpha}-linolenic acid; LXR, liver X receptor; OA, oleic acid; PAT, perilipin, ADRP, TIP-47; PPAR, peroxisome proliferator-activated receptor; PPRE, PPAR response element; RXR, retinoic X receptor; TIP-47, tail-interacting protein of 47 kDa


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