Transport of fatty acids across the placenta is vital for growth and development of the fetus. The placenta also plays an essential role in the development of preeclampsia, a disease associated with dyslipidemia, oxidative stress and inflammation. This thesis investigates the role of trophoblasts and placenta in lipid transport and storage in general, and in dyslipidemic pregnancies specifically.
The transport and uptake of fatty acids across trophoblast cells were studied in a placental cell line (BeWo). It was found that long-chain polyunsaturated fatty acids (LCPUFAs) are more efficiently transferred across these cells, and long term incubation with these fatty acids increases the general uptake of fatty acids compared with oleic acid. This suggests that LCPUFAs may function as regulators of fatty acid uptake by trophoblasts, which could have important implications for fetal nutrition and placental function.
The expression of several genes involved in fatty acid uptake and metabolism were analyzed. The expression of long-chain acyl-CoA synthetases (ACSL1 and 5) and the lipid droplet associated protein ADRP was increased by LCPUFAs, suggesting that these genes may be involved in the enhanced uptake of fatty acids mediated by LCPUFAs. Expression of these genes was also investigated in placenta from women with healthy pregnancies or preeclampsia. The expression of the transcription factor LXR, an important regulator of lipid metabolism, was decreased in preeclamptic placenta. ADRP was increased in preeclamptic placenta. ADRP expression in BeWo cells was increased by fatty acids (those elevated in the maternal circulation in preeclampsia) and by agents inducing oxidative stress. This suggests that placental ADRP could be regulated by both dyslipidemia and oxidative stress, and implies a role for ADRP in preeclamptic pregnancies. However, the exact function of ADRP and lipid droplets in placenta needs to be explored further.
List of Papers
Paper 1: Tobin KAR, Johnsen GM, Staff AC, Duttaroy AK. Long-chain polyunsaturated fatty acid transport across human placental choriocarcinoma (BeWo) cells. Placenta. 2009 Jan; 30(1):41-7.DOI: 10.1016/j.placenta.2008.10.007
Paper 2: Johnsen GM, Weedon-Fekjær MS, Tobin KAR, Staff AC, Duttaroy AK. Long-chain polyunsaturated fatty acids stimulate cellular fatty acid uptake in human placental choriocarcinoma (BeWo) cells. Placenta. 2009 Dec; 30(12):1037-1044.DOI: 10.1016/j.placenta.2009.10.004
Paper 3: Weedon-Fekjær MS, Johnsen GM, Sugulle M, Anthonisen EH, Nebb HI, Duttaroy AK, Staff AC. Expression of liver X receptors in pregnancies complicated by PE. Placenta. 2010 Sep;31(9):818-24.DOI: 10.1016/j.placenta.2010.06.015
Paper 4: Johnsen GM, Weedon-Fekjær MS, Tobin KAR, Sugulle M, Kliman HJ, Duttaroy AK, Staff AC. Increased Adipose Differentiation Related Protein (ADRP) expression in preeclamptic placenta. Submitted.