Brazilian Green Propolis Regulates Thermogenesis via Two Distinct Pathways

Brazilian green propolis (BGP), produced by honey bees, induces beige adipocyte formation and accelerates whole-body energy metabolism. Artepillin C (ArtC), the major cinnamic acid derivative of BGP, induces beige adipocyte formation and increases thermogenesis in inguinal white adipose tissue. However, the effects of BGP on beige adipocyte formation and energy metabolism remain unclear. Therefore, we aimed to examine the effects of BGP on beige adipocyte formation and thermogenesis. We used in vitro and in vivo approaches, such as cell culture and differentiation, component testing, thermogenesis measurement, and calcium influx assay. First, ArtC was confirmed to be a major BGP component contributing to beige adipocyte formation in vitro and in vivo. BGP-induced interscapular brown adipose tissue (iBAT) thermogenesis was not observed upon ArtC stimulation. Thereafter, inhibitory studies revealed that iBAT thermogenesis could be related to the transient receptor potential vanilloid 1 (TRPV1)-sympathetic nervous system channel. Finally, we identified culifolin, a cinnamic acid derivative of BGP, as an active component of this response, which activates calcium signaling in TRPV1-expressing cells. In addition, culifolin administration significantly increased the mouse iBAT temperature to the same extent as increased by BGP. Thus, BGP has a unique biological function in activating the two distinct pathways of brown-adipocyte and beige-adipocyte thermogenesis, contributing to increased energy expenditure.