Effect of non-equilibrium atmospheric pressure plasma (APP) on adipocyte browning via modulations of TRPV1 and TRPA1 channels

Complex mixtures of active agents produced by APP can regulate various cellular functions by triggering complex biochemical reactions, and APP thus emerges as being applicable to several clinical therapies. However, the details of the mechanisms underlying APP-inducible biological responses remain ill-defined. Recently, we revealed that exposure of 3T3L1 fibroblasts to APP-irradiated buffer raised cytoplasmic Ca²⁺ concentrations ([Ca²⁺]_c) by activating TRPV1 and TRPA1. We herein examined the effects of APP exposure on 3T3L1 adipocyte, focusing on its browning via APP-inducible TRPV1/A1 modulations. In 3T3L1 adipocytes, APP increased [Ca²⁺]_c. APP irradiation also increased browning-involved gene expressions, UCP1 and PRDM16. The siRNA-mediated silencing of TRPV1/A1 inhibited both the [Ca²⁺]_c transients and adipocyte browning, implying essential roles of these TRP channels in APP-inducible actions. Consistent with in vitro results, in vivo experiments on mice intraperitoneally injected with APP-irradiated buffer showed increased UCP1 mRNA expression in white adipose tissues, indicating promotion of their browning. These findings demonstrate that APP contributes to adipose tissue browning and suggest novel therapeutic applications benefiting energy homeostasis.