Eugenol promotes appetite through TRP channels mediated-CaMKK2/AMPK signaling pathway

Eugenol is a major component of clove oil. A recent study found that inhalation of eugenol promoted the appetite of mice. However, whether oral ingestion of eugenol promoted appetite is unclear and its mechanism await study. Here, mice were divided into four treatments (n = 20) and fed a basal diet supplemented with 0%, 0.005%, 0.01% and 0.02% eugenol for 4 weeks. In addition, mice (n = 7) were injected intraperitoneally with 3 mg/kg body weight eugenol. Our data showed that feeding mice with 0.01% and 0.02% eugenol promoted their appetite. In addition, the short-term intraperitoneal injection of eugenol enhanced the feed intake in mice within 1 h. Further studies found that dietary eugenol increased orexigenic factors expression and decreased anorexigenic factors expression in mice. We then carried out N38 cell experiments to explore the transient receptor potential (TRP) channels-dependent mechanism of eugenol in promoting appetite. We found that eugenol activated the TRP channels mediated-CaMKK2/AMPK signaling pathway in the hypothalamus and N38 cells. Besides, the inhibition of TRPV1 and AMPK eliminated the upregulation of eugenol on the agouti-related protein level in N38 cells. In conclusion, the study suggested that eugenol promotes appetite through TRPV1 mediated-CaMKK2/AMPK signaling pathway.