Session: SAT 649-659-Basic Mechanisms of Obesity
Poster Board SAT-659
Both centrally and peripherally expressed cannabinoid type 1 (CB1) receptors have been proposed to affect food intake, body weight and energy metabolism. Identifying the sites of action of CB1 receptors contributing to these effects is critical to understanding the effects of endogenous endocannabinoids and of exogenously added CB1 antagonists. In the present study, we have found that CB1 receptors are expressed in mouse enteroendocrine cells along with the gut hormones cholecystokinin and/or serotonin. The cannabinoid agonists anandamide and 2-arachidonoylglycerol elicited Ca++ responses in the STC-1 enteroendocrine cell line in a dose dependent fashion, and were blocked by the CB1 antagonist AM251. Administration of AM251 by gavage decreased both food and drink intake in wild type mice, but not in CB1 knockout mice. Our study suggests that CB1 receptors in enteroendocrine cells could be a site of action for cannabinoid effects on food intake, body weight and energy metabolism. Developing brain impermeable drugs that target CB1 receptors in enteroendocrine cells could have potential therapeutic effect on obesity by regulating release of gut hormones. This study was supported by NIH grant NIDDK R01DK081421 to RFM.
Nothing to Disclose: YL, MR, KR, DR, BM, RM
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