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| Status |
Public on Oct 14, 2016 |
| Title |
Lysophosphatidylcholines activate PPARδ and protect human skeletal muscle cells from lipotoxicity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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 10 µM LPC for 24 h 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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| Overall design |
Human myotubes from four different donors were treated with 10 µM LPC(16:0) or LPC(18:1) or solvent for 24 h
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| Contributor(s) |
Klingler C, Zhao X, Adhikary T, Li J, Xu G, Häring H, Schleicher E, Lehmann R, Weigert C |
| Citation missing |
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| Submission date |
Jan 28, 2016 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Christian Klingler |
| E-mail(s) |
christian.klingler@unibas.ch
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| Organization name |
IDM at the University Hospital Tuebingen
|
| Department |
Medical Clinic IV
|
| Lab |
Pathobiochemistry
|
| Street address |
Otfried-Mueller Street 10
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| City |
Tuebingen |
| ZIP/Postal code |
72076 |
| Country |
Germany |
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| Platforms (1) |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA310091 |
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