β-Caryophyllene, a dietary phytocannabinoid, alleviates high-fat diet-induced hepatic steatosis in mice via AMPK activation

beta-Caryophyllene (BCP), a dietary phytocannabinoid, significantly suppresses palmitate-induced lipid accumulation in human HepG2 hepatocytes via activation of AMP-activated protein kinase (AMPK) signaling. The objective of the preset research was to assess whether oral administration of BCP alleviates obesity-induced hepatic steatosis in mice through AMPK activation. We examined the protective action of supplementation of 0.3% BCP (w/w) in a high-fat diet (HFD) on C57BL/6J mice for 12 weeks. BCP supplementation evidently ameliorated histological hepatic steatosis features, and significantly reduced triglycerides and cholesterol levels in the liver, and serum levels of aspartate aminotransferase and alanine aminotransferase as compared with non-supplemented HFD-fed mice. Immunoblotting revealed that BCP supplementation in HFD-fed mice also caused hepatic AMPK activation. Furthermore, treatment with BCP in HFD-fed mice significantly suppressed body weight gain and attenuated obesity-related phenotypes relative to the HFD mice. Our results suggest the usefulness of BCP in the prevention of obesity-related liver steatosis and liver injury. Graphical Abstract beta-Caryophyllene supplementation ameliorates obesity-related liver steatosis and liver injury in high-fat diet-fed mice.