Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1861, Issue 12, Pages 1980-1992Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2016.09.020
Keywords
Lysophospholipids; Nuclear receptors/lipid ligands; Transcription; Skeletal muscle; Diabetes; Human myotubes; AMPK
Funding
- Deutsche Forschungsgemeinschaft [GRK 1302-2]
- German Federal Ministry of Education and Research (BMBF) [01GI0925]
- Key Foundation and Creative Research Group Project (NSFC) [21435006, 21321064]
- Sino-German Center for Research Promotion (DFG) [GZ 753, LE 1391/1-1]
- Sino-German Center for Research Promotion (NSFC) [GZ 753]
Ask authors/readers for more resources
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 mu M 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 PPAR delta antagonist GSK0660 or GSK3787. The induction of PDK4 by LPCs was blocked with siRNA against PPARD. The activation of PPAR delta transcriptional activity by LPC was shown as PPAR delta-dependent luciferase reporter gene expression and enhanced DNA binding of the PPAR delta/RXR dimer. On a functional level, further results show that the LPC-mediated activation of PPAR delta 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 PPAR delta antagonist GSK0660. Taking together, LPCs can activate PPAR delta, which is consistent with the association of high plasma LPC levels and PPAR delta-dependent anti-diabetic and anti-inflammatory effects. (C) 2016 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available