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PMID:20219900

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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

Significance

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

See also

References

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