Endocrine Abstracts

The browning of white adipocytes can increase energy expenditure through the activity of uncoupling protein 1 (UCP1) located on the mitochondrial inner membrane. The endocannabinoid (EC) system, composed of endogenous cannabinoids and cannabinoid receptors, has been shown to regulate energy balance in the body. A previous research has demonstrated that blocking the cannabinoid type 1 receptor (CB1R) causes white adipocyte browning. However, the mechanism of the EC system regulating white adipocyte browning was still not elucidated. 2-Arachidonoylglycerol (2-AG), one of the endogenous endocannabinoids, can activate CB1R and CB2R. Our results showed that treatment with 2-AG in 3T3-L1 adipocytes could increase expressions of adipocyte browning markers, including UCP1, PRDM16, and PGC1α. The 2-AG-induced upregulation of browning markers was substantially abolished by pretreatment with a CB2R antagonist. These findings suggested that CB2 activation could induce white adipocyte browning. JWH133, a CB2R agonist, also decreased lipid droplets’ diameter in 3T3-L1 adipocytes. Based on the results of Seahorse XF Mito stress test, we found that the mitochondrial respiration function of 3T3-L1 adipocytes was increased when treated with JWH133. Furthermore, one-week JWH133 subcutaneously infusion (0.2 mg/kg/day) caused weight reduction in both epididymal adipose tissues (eWAT) and inguinal adipose tissues (iWAT) in mice. Additionally, a reduction in adipocyte size in iWAT was also observed. It also enhanced UCP1 protein levels and UCP1 immunoreactivity signal in iWAT. In coclusion, our studies demonstrated that activation of CB2 receptors could induce white adipocyte browning in vitro and in vivo. These finding provide a novel perspective for the clinical application of CB2 in promoting energy metabolism to treat obesity and associated diseases.