Faculty of Medicine, University of Oslo, and Department of Endocrinology, Oslo University Hospital, Oslo, Norway.
J Lipid Res. 2010 Jul;51(7):1886-96. doi: 10.1194/jlr.M004978. Epub 2010 Mar 10.
Placental fatty acid transport and metabolism are important for proper growth and development of the feto-placental unit. The nuclear receptors, liver X receptors alpha and beta (LXRalpha and LXRbeta), are key regulators of lipid metabolism in many tissues, but little is known about their role in fatty acid transport and metabolism in placenta. The current study investigates the LXR-mediated regulation of long-chain acyl-CoA synthetase 3 (ACSL3) and its functions in human placental trophoblast cells. We demonstrate that activation of LXR increases ACSL3 expression, acyl-CoA synthetase activity, and fatty acid uptake in human tropholast cells. Silencing of ACSL3 in these cells attenuates the LXR-mediated increase in acyl-CoA synthetase activity. Furthermore, we show that ACSL3 is directly regulated by LXR through a conserved LXR responsive element in the ACSL3 promoter. Our results suggest that LXR plays a regulatory role in fatty acid metabolism by direct regulation of ACSL3 in human placental trophoblast cells.
胎盘脂肪酸的转运和代谢对于胎儿-胎盘单位的正常生长和发育非常重要。核受体肝 X 受体α和β(LXRα和 LXRβ)是许多组织中脂质代谢的关键调节剂,但它们在胎盘脂肪酸转运和代谢中的作用知之甚少。本研究探讨了 LXR 对长链酰基辅酶 A 合成酶 3(ACSL3)的调节作用及其在人胎盘滋养层细胞中的功能。我们证明,LXR 的激活增加了人滋养层细胞中 ACSL3 的表达、酰基辅酶 A 合成酶活性和脂肪酸摄取。在这些细胞中沉默 ACSL3 会减弱 LXR 介导的酰基辅酶 A 合成酶活性增加。此外,我们表明 ACSL3 通过 ACSL3 启动子中的保守 LXR 反应元件直接受 LXR 调节。我们的结果表明,LXR 通过直接调节人胎盘滋养层细胞中的 ACSL3 在脂肪酸代谢中发挥调节作用。