PMID:20219900

Citation	Weedon-Fekjaer, MS, Dalen, KT, Solaas, K, Staff, AC, Duttaroy, AK and Nebb, HI (2010) Activation of LXR increases acyl-CoA synthetase activity through direct regulation of ACSL3 in human placental trophoblast cells. J. Lipid Res. 51:1886-96
Abstract	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.
Links	PubMed PMC2882745 Online version:10.1194/jlr.M004978
Keywords	Animals; Base Sequence; Cell Line; Coenzyme A Ligases/genetics; Coenzyme A Ligases/metabolism; Fatty Acids/metabolism; Female; Humans; Microarray Analysis; Molecular Sequence Data; Orphan Nuclear Receptors/agonists; Orphan Nuclear Receptors/genetics; Orphan Nuclear Receptors/metabolism; Placenta/cytology; Placenta/metabolism; Pregnancy; Sequence Alignment; Trophoblasts/cytology; Trophoblasts/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:ACSL3	acts_upstream_of	GO:0044539: long-chain fatty acid import into cell	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:ACSL3	enables	GO:0004467: long-chain fatty acid-CoA ligase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F	occurs_in:(UBERON:0001987)	Seeded From UniProt	complete
HUMAN:RXRA	enables	GO:0004879: nuclear receptor activity	ECO:0000314: direct assay evidence used in manual assertion		F	has_input:(UniProtKB:O95573)	Seeded From UniProt	complete
HUMAN:RXRA	involved_in	GO:0045944: positive regulation of transcription by RNA polymerase II	ECO:0000314: direct assay evidence used in manual assertion		P	has_input:(UniProtKB:O95573)	Seeded From UniProt	complete
HUMAN:RXRA	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q13133	F		Seeded From UniProt	complete
HUMAN:NR1H2	involved_in	GO:0045944: positive regulation of transcription by RNA polymerase II	ECO:0000314: direct assay evidence used in manual assertion		P	has_input:(UniProtKB:O95573)	Seeded From UniProt	complete
HUMAN:NR1H3	involved_in	GO:0045944: positive regulation of transcription by RNA polymerase II	ECO:0000314: direct assay evidence used in manual assertion		P	has_input:(UniProtKB:O95573)	Seeded From UniProt	complete
HUMAN:NR1H3	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P19793	F		Seeded From UniProt	complete
HUMAN:NR1H2	involved_in	GO:0045944: positive regulation of transcription by RNA polymerase II	ECO:0000314: direct assay evidence used in manual assertion		P	has_regulation_target:(UniProtKB:O95573)	Seeded From UniProt	complete
HUMAN:NR1H3	involved_in	GO:0045944: positive regulation of transcription by RNA polymerase II	ECO:0000314: direct assay evidence used in manual assertion		P	has_regulation_target:(UniProtKB:O95573)	Seeded From UniProt	complete

References

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