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

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

Department of nutrition, University of Oslo, Oslo N-0316

Corresponding Author: 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 towards long-chain polyunsaturated fatty acids (LCPUFA) has been demonstrated. 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 (BeWo) cell line, and in primary human trophoblasts. LCPUFAs of the n-3 and n-6 series (arachidonic acid (AA, 20:4n-6), docosahexaenoic acid (DHA, 22:6n-3), and eicosapentaenoic acid (EPA, 20:5n-3)) were more efficient than shorter fatty acids in stimulating ADRP mRNA expression. The fatty acid mediated increase in ADRP mRNA expression was not related to the differentiation state of the cells. Synthetic PPAR and RXR 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, increase the cellular content of radiolabelled 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.

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