Approximately, 72% of Americans aged 20 or older are considered overweight or obese. Despite numerous therapies currently used in the treatment of obesity (lifestyle changes and pharmacological/surgical interventions), there is still a need for improved long-term weight management. Investigations of the brain’s regulation of food intake may lead to the discovery of novel, more efficacious therapeutic treatments . Cocaine- and Amphetamine-regulated transcript (CART) is an endogenous neuropeptide produced in the CNS and exerts anorectic effects by inhibiting food intake. A recent study identified the orphan G-protein coupled receptor, Gpr160 as the  CART receptor. Gpr160 is abundantly expressed in the brainstem, a CNS site of action for CART mediated energy balance. Thus, we hypothesized that CART activation of Gpr160 signaling underlies the intake suppressive effects of CART acting in the brainstem. To test our hypothesis, we utilized a viral-mediated strategy to target Gpr160 selectively in the brainstem. Male Sprague Dawley rats received a bilateral infusion of either a AAV-GFP (control; n=6) or AAV-miGpr160-GFP (Gpr160-KD; n=7) into the nucleus tractus solitarius (a prominent nucleus in the brainstem). First, in order to investigate how the knockdown of Gpr160 in brainstem affects food intake and body weight,  rats were given ad-libitum access to chow diet for 18 days then switched to a 60% high fat diet (HFD) for an additional 12 days. Using an automated feedometer, food intake was recorded on a second-by-second basis and body weights were recorded every 48-hour. Across the chow and HFD phases of the experiment, we did not observe a statistically significant difference between the control and Gpr160-KD group in either cumulative food intake or change in body weight. We did observe a slight, non-significant, shift in the diurnal feeding behavior of the Gpr160-KD compared to the control group. 

Next, we examined the role of Gpr160 on the intake suppressive effects of Exendin 4(Ex4); a glucagon-like peptide 1 (Glp1) agonist that potently suppresses food intake and is FDA-approved for the treatment of diabetes and obesity. Several studies revealed an interaction between GLP1 and CART regulation of energy balance. To test the hypothesis that Gpr160 compromise would attenuate the ability of Ex4 to suppress food intake, rats received intraperitoneal injections of either saline (1ml/kg) or Ex4 (3μg/ml/kg) just prior to lights out. HFD intake and body weight was recorded for 24 hours. . We observed a significant decrease in cumulative food intake as a result of Ex4, irrespective of viral treatment. This finding suggests that Gpr160 is not required for Ex4’s anorectic effects at the level of the brainstem. In conclusion, our experiments did not produce evidence for brainstem Gpr160 in the regulation of either chow or HFD food intake. These negative findings could be attributed to an insufficient degree of Gpr160-KD,  underpowered experiments, or perhaps the brainstem is not a primary site of action for CART-induced satiety. Future studies should examine other regions of the brain as well as other neuropeptides known to be involved in CART-mediated energy balance.