Amey Dhopeshwarkar, Ph.D. of the Mackie Lab at Indiana University Bloomington will present a lecture entitled: Δ9THC, a major component of cannabis, and its metabolites, bind and activate GPR119 to induce weight loss in diet induced obese mice.
Abstract: User anecdotes and several pre-clinical/clinical studies suggest that cannabis intake promotes increase in consumption of calorie rich food (aka “munchies”). In regular cannabis users, this behavior, along with a sedentary lifestyle would be expected to promote weight gain, obesity, a worsening of metabolic parameter and an increased risk for type 2 diabetes. However, several epidemiological studies indicate otherwise: Chronic cannabis users are modestly protected from obesity and type II diabetes when compared with non-users. THC and cannabidiol are major components of cannabis and thus may play an important role in protecting cannabis users from obesity. In this study, we show that THC and its metabolites bind and activate a lipid-sensing receptor, GPR119, in vitro with distinctive functional selectivity. Furthermore, THC induces GLP1 secretion from murine enteroendocrine GLUTag cells. In vivo, oral and parenteral treatment with THC promotes weight loss in wildtype diet induced obese (DIO) mice. This effect is absent in GPR119 knock out mice. Cannabidiol failed to activate GPR119 in vitro and had no weight loss promoting effects in DIO mice. These results indicate a novel role of THC and its metabolites in promoting weight loss via GPR119.