Format

Send to

Choose Destination
J Lipid Res. 2015 Feb;56(2):254-65. doi: 10.1194/jlr.M052464. Epub 2014 Dec 15.

Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α.

Author information

1
Laboratory of Molecular Functions of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
2
Laboratory of Molecular Functions of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan Research Unit for Physiological Chemistry, Kyoto University, Kyoto 606-8501, Japan.
3
Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan.
4
Nara Women's University, Nara 630-8506, Japan.

Abstract

PPARα is well known as a master regulator of lipid metabolism. PPARα activation enhances fatty acid oxidation and decreases the levels of circulating and cellular lipids in obese diabetic patients. Although PPARα target genes are widely known, little is known about the alteration of plasma and liver metabolites during PPARα activation. Here, we report that metabolome analysis-implicated upregulation of many plasma lysoGP species during bezafibrate (PPARα agonist) treatment. In particular, 1-palmitoyl lysophosphatidylcholine [LPC(16:0)] is increased by bezafibrate treatment in both plasma and liver. In mouse primary hepatocytes, the secretion of LPC(16:0) increased on PPARα activation, and this effect was attenuated by PPARα antagonist treatment. We demonstrated that Pla2g7 gene expression levels in the murine hepatocytes were increased by PPARα activation, and the secretion of LPC(16:0) was suppressed by Pla2g7 siRNA treatment. Interestingly, LPC(16:0) activates PPARα and induces the expression of PPARα target genes in hepatocytes. Furthermore, we showed that LPC(16:0) has the ability to recover glucose uptake in adipocytes induced insulin resistance. These results reveal that LPC(16:0) is induced by PPARα activation in hepatocytes; LPC(16:0) contributes to the upregulation of PPARα target genes in hepatocytes and the recovery of glucose uptake in insulin-resistant adipocytes.

KEYWORDS:

liver; lysoglycerophospholipid; mass spectrometry; omics; phospholipases/A2

PMID:
25510248
PMCID:
PMC4306680
DOI:
10.1194/jlr.M052464
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center