Methyl Cinnamate Inhibits Adipocyte Differentiation via Activation of the CaMKK2 AMPK Pathway in 3T3-L1 Preadipocytes

Methyl cinnamate, an active component of Zanthoxylurn armatum, is a widely used natural flavor compound with antimicrobial and tyrosinase inhibitor activities. However, the underlying bioactivity and molecular mechanisms of methyl cinnamate on adipocyte function and metabolism remain unclear. The aim of this study was to investigate the inhibitory effect of methyl cinnamate on adipogenesis in 3T3-L1 preadipocytes. Methyl cinnamate markedly suppressed triglyceride accumulation associated with down-regulation of adipogenic transcription factor expression, including sterol regulatory element binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor gamma (PPAR gamma), and CCAAT/enhancer-binding protein a (Cl EBP alpha). Additionally, methyl cinnamate-inhibited PPAR gamma activity and adipocyte differentiation were partially reversed by the PPAR gamma agonist troglitazone. Furthermore, methyl cinnamate stimulated Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and phospho-AMP-activated protein kinase (AMPK) expression during adipogenesis. This study first revealed methyl cinnamate has antiadipogenic activity through mechanisms mediated, in part, by the CaMKK2 AMPK signaling pathway in 3T3-L1 cells.