Abstract

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.

Highlights

  • A therapeutic device to expose the human body to high-voltage electric potential (HELP) was approved by the Ministry of Health, Labour and Welfare in Japan

  • capillary electrophoresis (CE)- and liquid chromatography (LC)-time-of-flight mass spectrometry (TOFMS) analyses were used to measure the abundance of a total of 161 metabolites in the plasma obtained from healthy participants

  • 31 metabolites were significantly upregulated after HELP exposure which included fatty acid amides (OEA, palmitoylethanolamide, and stearoylethanolamide); fatty acids [oleic acid, linoleic acid, linolenic acid, cis-4,7,10,13,16,19-docosahexaenoic acid, cis-5,8,11,14,17-eicosapentaenoic acid, cis-8,11,14-eicosatrienoic acid, cis-11,14-eicosadienoic acid, cis-11-eicosenoic acid, arachidonic acid, ethyl arachidonate, nervonic acid, FA(22:5), FA(22:4), FA(19:1), FA(17:0), FA(14:0), palmitic acid, stearic acid, and heptadecanoic acid]; amino acids; steroids; UDP; 2-hydroxybutyric acid; and threonic acid

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Summary

Introduction

A therapeutic device to expose the human body to high-voltage electric potential (HELP) was approved by the Ministry of Health, Labour and Welfare in Japan. High-voltage electric field (EF) therapy is reportedly an effective treatment for stiff shoulders, constipation, insomnia and headache, while the effects of EF exposure on several blood parameters and liver diacylglycerol acyltransferase-2 (DGAT2) mRNA expression have been described [1,2,3]. Much of the evidence regarding the effect of EF was based on manipulations involving immobilization stress using experimental animals. It remains unclear whether the observations following EF exposure were derived individually from EF exposure or in conjunction with immobilization stress. The results of these studies suggest that HELP exposure may present an alternative therapy for several conditions, the mechanisms remain elusive

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