Artepillin C, a Key Component of Brazilian Propolis, Induces Thermogenesis in Inguinal White Adipose Tissue of Mice through a Creatine-Metabolism-Related Thermogenic Pathway

Induction of beige adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity because beige adipocytes release excess energy via uncoupling-protein-1-associated thermogenesis. In this study, we investigated how artepillin C (ArtC) promotes thermogenesis in vivo. We demonstrated that 28 day administration of ArtC (10 mg/kg of body weight) to mice significantly induced thermogenesis in beige adipocytes in inguinal WAT (iWAT) and suppressed reductions in core body temperature induced by cold exposure at 4 °C. Moreover, ArtC-induced thermogenesis in iWAT was significantly inhibited by treatment with a creatine metabolism inhibitor, and ArtC significantly upregulated the expression of creatine-metabolism-related enzymes in the thermogenic pathway. These results indicate that ArtC induces thermogenesis in beige adipocytes in iWAT, and the observed ArtC-induced thermogenesis is associated with the creatine-metabolism-related thermogenic pathway, which is characteristically observed in beige adipocytes.