Lysophosphatidylcholines activate PPAR delta and protect human skeletal muscle cells from lipotoxicity

doi:10.1016/j.bbalip.2016.09.020

	Lysophosphatidylcholines activate PPAR delta and protect human skeletal muscle cells from lipotoxicity
	Haring, Hans-Ulrich 2,3,4; Klingler, Christian 2,3,4; Zhao, Xinjie 1; Adhikary, Till 5; Li, Jia 1; Xu, Guowang 1; Schleicher, Erwin 2; Lehmann, Rainer 2,3,4; Weigert, Cora 2,3,4
刊名	BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
	2016-12-01
卷号	1861 期号:12 页码:1980-1992
关键词	Lysophospholipids Nuclear Receptors/lipid Ligands Transcription Skeletal Muscle Diabetes Human Myotubes Ampk
ISSN号	1388-1981
DOI	10.1016/j.bbalip.2016.09.020
文献子类	Article
英文摘要	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.
WOS关键词	INSULIN-RESISTANCE ; ENDOTHELIAL-CELLS ; RECEPTOR DELTA ; FATTY-ACIDS ; EXPRESSION ; METABOLISM ; PLASMA ; IDENTIFICATION ; RECRUITMENT ; BETA/DELTA
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000388546000011
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/169782]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Weigert, Cora
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, 457 Zhongshan Rd, Dalian 116023, Peoples R China 2.Univ Tubingen, Div Pathobiochem & Clin Chem, Otfried Muller Str 10, D-72076 Tubingen, Germany 3.Univ Tubingen, Inst Diabet Res & Metab Dis, Helmholtz Zentrum Munchen, Otfried Muller Str 10, D-72076 Tubingen, Germany 4.German Ctr Diabet Res DZD, Ingolstadter Landstr 1, D-85764 Munich, Germany 5.Philipps Univ, Inst Mol Biol & Tumor Res IMT, Ctr Tumor Biol & Immunol ZTI, Hans Meerwein Str 3, D-35043 Marburg, Germany
推荐引用方式 GB/T 7714	Haring, Hans-Ulrich,Klingler, Christian,Zhao, Xinjie,et al. Lysophosphatidylcholines activate PPAR delta and protect human skeletal muscle cells from lipotoxicity[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,2016,1861(12):1980-1992.
APA	Haring, Hans-Ulrich.,Klingler, Christian.,Zhao, Xinjie.,Adhikary, Till.,Li, Jia.,...&Weigert, Cora.(2016).Lysophosphatidylcholines activate PPAR delta and protect human skeletal muscle cells from lipotoxicity.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,1861(12),1980-1992.
MLA	Haring, Hans-Ulrich,et al."Lysophosphatidylcholines activate PPAR delta and protect human skeletal muscle cells from lipotoxicity".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS 1861.12(2016):1980-1992.