Weight loss induced by blocking CB1 cannabinoid receptors is associated with an altered microRNA profile and suppression of inflammation in adipose tissue (IRM9P.458)

Abstract

Abstract Obesity is associated with chronic inflammation. Cells of the immune system express cannabinoid CB1 and CB2 receptors, the activation of which triggers anti-inflammatory effects. We investigated the effect of treatment of mice with SR141716A, a cannabinoid receptor1 (CB1) antagonist, on Diet-Induced Obesity (DIO), specifically whether such a treatment can induce anti-inflammatory state in adipose tissue. DIO model was generated by feeding C57BL/6J mice with high-fat diet (HFD) whereas their lean, age-matched controls were fed low-fat diet (LFD). HFD-fed mice were treated with either SR141716A (10mg/kg/day) or vehicle by daily oral gavage for 4 weeks starting at week 12. To assess the effect of SR141716A beyond its effect on weight loss and diet intake, pair-feeding was conducted in diet-intake matched controls and diet intake was adjusted in body-weight-matched controls. Our data demonstrated that SR141716A suppressed diet intake transiently however weight loss and reduction in fat mass was persistent. High throughput miR analysis showed that SR141716A skewed adipose tissue macrophage balance to more anti-inflammatory macrophages. Induction of myeloid-derived-suppressive cells and TH2 cells followed by suppression of pro-inflammatory macrophages were observed in SR141716A-treated HFD-fed group. Together, this study demonstrates that CB1 receptor blockade affects miR expression that induces anti-inflammatory state in adipose tissue independent of calorie intake inhibition.