Targeted lipidomics reveals changes in N-acyl serines by acute exposure to an electric field: Molecular insights into the docking of N-18:1 serine interaction with TRPV1 or PPAR-α

Abstract

Alternative therapy with medical devices using high-voltage electric potential (HELP) to generate an electric field (EF) is common in Japan. However, the mechanisms underlying potential health benefits of this therapy remain unclear. Therefore, we investigated the effect of HELP exposure (9 kV /electrode + 9 kV/electrode, 30 min) on N-acyl serines (N-acyl SERs) using selected reaction monitoring (SRM) analysis in plasma samples obtained from healthy human subjects before and after a single treatment session. N-18:1 SER, and N-16:0 SER were significantly upregulated following HELP exposure. Under these conditions, HELP exposure did not exert on levels of N-18:0 SER, N-18:2 SER, N-20:4 SER, and N-22:6 SER. Because N-18:1 ethanolamine (N-18:1 EA) is known to activate, transient receptor potential vanilloid 1 (TRPV1) and peroxisome proliferator-activated receptor-alpha (PPAR-α), we further examined an in silico docking simulation with TRPV1 and PPAR-α. The binding energies with TRPV1 were -6.359 and -6.227 kcal/mol for N-18:1 SER and N-18:1 EA, respectively. The binding energies with PPAR-α were -7.366 and -6.956 kcal/mol for N-18:1 SER and N-18:1 EA, respectively. In human HepG2 cells, N-18:1 SER enhanced fatty acid-binding protein 1 (FABP1) mRNA expression. N-18:1 SER-induced FABP1 mRNA expression was sensitive to the PPAR-α antagonist GW6471. Our findings provide new insights into the molecular mechanisms of the health benefits of EF therapy. Abbreviations: ACOX1: peroxisomal acyl-coenzyme A oxidase 1; DSPS: delayed sleep phase syndrome; EC50: half maximal effective concentration; EF: electric field; FA: fatty acid; FABP1: fatty acid-binding protein 1; HELP: high-voltage electric potential; HODE: hydroxyoctadecadienoic acid; IL: interleukin; MSL: multiple benign symmetric lipomatosis; N-18:2 EA: N-linoleoyl ethanolamine; N-18:1 EA: N-oleoyl ethanolamine; N-16:0 EA: N-palmitoyl ethanolamine; N-18:0 EA: Nstearoyl ethanolamine; NF-κB: nuclear factor-kappa B; NLRP3: nodlike receptor protein 3; N-20:4 SER: N-arachidonyl serine; N-22:6 SER: N-docosahexaenoyl serine; N-18:2 SER: N-linoleoyl serine; N-18:1 SER: N-oleoyl serine; N-16:0 SER: N-palmitoyl serine; N-18:0 SER: N-stearoyl serine; PLAAT: phospholipase A/acyltransferase; PLA2: phospholipase A2; PPAR-α: peroxisome proliferator-activated receptoralpha; qRT-PCR: quantitative real-time polymerase chain reaction; SRM: selected reaction monitoring; TLR4: toll-like receptor 4; TRPV1: transient receptor potential vanilloid 1.