Upregulation of the expression of inflammatory and angiogenic markers in human adipocytes by a synthetic cannabinoid, JTE-907

Abstract

Inflammation in adipose tissue is a characteristic of obesity and the metabolic syndrome. It is suggested that the endocannabinoid system is involved in the regulation of infl ammatory and angiogenic processes within the tissue. Human subcutaneous preadipocytes (Zen Bio) were used as the source of human preadipocytes or adipocytes. Gene expression was examined by RT-PCR and real-time PCR. The secretion of infl ammation-related proteins was determined by an ELISA array. In experiments on adipocytes treated at day 14 post-diff erentiation, JTE-907, a synthetic cannabinoid, upregulated the expression of key infl ammatory markers – IL-6, MCP-1 and IL-1 β – and angiogenic factors – VEGF and ANGPTL4 – at 10 μ M after 20 h of treatment, having also increased the expression of TRPV1 at 10 μ M. JTE-907 showed no eff ect after 4 h. The ELISA array showed a 2.6-fold increase in IL-6 protein release. The eff ect of JTE-907 was inhibited by AM251 (CB 1 antagonist), and partially by arachidonyl serotonin (TRPV1 and FAAH antagonist). The CB 2 antagonist, AM630, partially upregulated the eff ect of JTE-907. Preadipocytes fed 14 days after 100 % confl uence exhibited downregulation of CB 1 , MCP-1, and IL-1 β , 20 h after having been exposed to JTE-907. CB 1 and TRPV1 receptors participate in the regulation of several infl ammatory and angiogenic factors in human adipocytes, indicating their potential value as targets for the treatment of disorders related to obesity.