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

PPAR is well known as a master regulator of lipid metabolism. PPAR activation enhances fatty acid oxidation and decreases the levels of circulating and cellular lipids in obese diabetic patients. Although PPAR target genes are widely known, little is known about the alteration of plasma and liver metabolites during PPAR activation. Here, we report that metabolome analysis-implicated upregulation of many plasma lysoGP species during bezafibrate (PPAR 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 PPAR activation, and this effect was attenuated by PPAR antagonist treatment. We demonstrated that Pla(2)g7 gene expression levels in the murine hepatocytes were increased by PPAR activation, and the secretion of LPC(16:0) was suppressed by Pla(2)g7 siRNA treatment. Interestingly, LPC(16:0) activates PPAR and induces the expression of PPAR 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 PPAR activation in hepatocytes; LPC(16:0) contributes to the upregulation of PPAR target genes in hepatocytes and the recovery of glucose uptake in insulin-resistant adipocytes.