title: Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α.
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.
authors.affiliation: Laboratory of Molecular Functions of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Haruya
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.affiliation: Laboratory of Molecular Functions of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Yota
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Laboratory of Molecular Functions of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kamakari
authors.affiliation: Laboratory of Molecular Functions of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Hirata
authors.affiliation: Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shibata
authors.affiliation: Nara Women's University, Nara 630-8506, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakata
authors.affiliation: Nara Women's University, Nara 630-8506, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inoue
authors.affiliation: 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.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008244:Lysophosphatidylcholines / Q000097:blood* / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D051379:Mice; D047493:PPAR alpha / Q000097:blood* / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: D008244:Lysophosphatidylcholines; D047493:PPAR alpha; D034741:RNA, Small Interfering; C006065:We 201; D001629:Bezafibrate
keywords: liver; lysoglycerophospholipid; mass spectrometry; omics; phospholipases/A2