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Lysophosphatidylcholines activate PPARδ and protect human skeletal muscle cells from lipotoxicity.
Biochim. Biophys. Acta 1861, 1980-1992 (2016)
Metabolomics studies of human plasma demonstrate a correlation of lower plasma lysophosphatidylcholines (LPC) concentrations with insulin resistance, obesity, and inflammation. This relationship is not unraveled on a molecular level. Here we investigated the effects of the abundant LPC(16:0) and LPC(18:1) on human skeletal muscle cells differentiated to myotubes. Transcriptome analysis of human myotubes treated with 10μM LPC for 24h revealed enrichment of up-regulated peroxisome proliferator-activated receptor (PPAR) target transcripts, including ANGPTL4, PDK4, PLIN2, and CPT1A. The increase in both PDK4 and ANGPTL4 RNA expression was abolished in the presence of either PPARδ antagonist GSK0660 or GSK3787. The induction of PDK4 by LPCs was blocked with siRNA against PPARD. The activation of PPARδ transcriptional activity by LPC was shown as PPARδ-dependent luciferase reporter gene expression and enhanced DNA binding of the PPARδ/RXR dimer. On a functional level, further results show that the LPC-mediated activation of PPARδ can reduce fatty acid-induced inflammation and ER stress in human skeletal muscle cells. The protective effect of LPC was prevented in the presence of the PPARδ antagonist GSK0660. Taking together, LPCs can activate PPARδ, which is consistent with the association of high plasma LPC levels and PPARδ-dependent anti-diabetic and anti-inflammatory effects.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Ampk ; Diabetes ; Human Myotubes ; Lysophospholipids ; Nuclear Receptors/lipid Ligands ; Skeletal Muscle ; Transcription; Insulin-resistance; Endothelial-cells; Receptor Delta; Fatty-acids; Expression; Metabolism; Plasma; Identification; Recruitment; Beta/delta
ISSN (print) / ISBN
0006-3002
Zeitschrift
Biochimica et Biophysica Acta
Quellenangaben
Band: 1861,
Heft: 12,
Seiten: 1980-1992
Verlag
Elsevier
Verlagsort
Amsterdam
Nichtpatentliteratur
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