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,Asim K Duttaroy

doi:10.1194/jlr.m500527-jlr200

Abstract

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.

Highlights

Transplacental transfer of maternal fatty acids is critical for fetal growth and development
The BeWo cell line is a human placental choriocarcinoma cell line that has been used to study lipid metabolism and has maintained several of the characteristics of the natural trophoblasts [35]. We used this cell line as a model system to mimic the effects of fatty acids in trophoblasts; in addition, we compared the effects in BeWo cells using isolated primary human trophoblasts
We used serum-free medium containing 1% BSA, and we observed lower basal mRNA expression, but the fatty acid-mediated effect was the same as in serum-containing medium (Fig. 1B). These results indicate a tendency toward LCPUFAs (AA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)) being more potent at Regulation of Adipose differentiation-related protein (ADRP) by long-chain polyunsaturated fatty acids 817 inducing ADRP mRNA than shorter chain fatty acids (OA, a-LN, and g-LN) (Fig. 1B)

Summary

Introduction

Transplacental transfer of maternal fatty acids is critical for fetal growth and development. Dose-dependent effect of fatty acid-mediated ADRP mRNA and protein expression We investigated the effects of fatty acids and nuclear receptor agonists on ADRP protein expression.

Results

Conclusion