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 inflammatory 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 inflammation-related proteins was determined by an ELISA array. In experiments on adipocytes treated at day 14 post-differentiation, JTE-907, a synthetic cannabinoid, upregulated the expression of key inflammatory markers – IL-6, MCP-1 and IL-1β – and angiogenic factors – VEGF and ANGPTL4 – at 10 μM after 20 h of treatment, having also increased the expression of TRPV1 at 10 μM. JTE-907 showed no effect after 4 h. The ELISA array showed a 2.6-fold increase in IL-6 protein release. The effect of JTE-907 was inhibited by AM251 (CB1 antagonist), and partially by arachidonyl serotonin (TRPV1 and FAAH antagonist). The CB2 antagonist, AM630, partially upregulated the effect of JTE-907. Preadipocytes fed 14 days after 100% confluence exhibited downregulation of CB1, MCP-1, and IL-1β, 20 h after having been exposed to JTE-907. CB1 and TRPV1 receptors participate in the regulation of several inflammatory and angiogenic factors in human adipocytes, indicating their potential value as targets for the treatment of disorders related to obesity.

Key words

endocannabinoid system - inflammation - human adipose tissue - obesity - TRPV1 - CB1

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