Non-targeted human plasma metabolomics reveals the changes in oleoylethanolamide, a lipid-derived signaling molecule, by acute exposure of electric field

Medical treatment using high-voltage electric potential (HELP) device to generate an electric field (EF) is an alternative therapy commonly used in Japan. However, little is known about the underlying mechanisms of the potential benefits to health. The identification of EF exposure -related biomarkers is key to understanding the beneficial effects of EF therapy. We screened plasma metabolites obtained prior to and immediately after HELP exposure (18 kV, 30 min) in 10 healthy human subjects by via non-targeted plasma metabolomic analysis. Among 161 metabolites, several fatty acid amides containing a signaling molecule oleoylethanolamide (OEA) and fatty acids were significantly upregulated. Under these conditions, HELP exposure had no effect on citric acid and ornithine cycle intermediates. Because OEA is known to induce lipolysis as a putative endogenous ligand of peroxisome proliferator-activated receptor (PPAR)-α, we further confirmed the effect of OEA on gene expression using human subcutaneous cultured adipocytes. Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) mRNA was upregulated by OEA treatment. OEA-induced ACOX1 mRNA expression was sensitive to a PPAR-α antagonist GW6471. Our findings will provide the new insights into the molecular mechanisms of EF therapy.