12357 Ptp1b In The Reward System Promotes Rewarding Effects Of A High-fat Diet
Authors: Banno Ryoichi , Kuno Mitsuhiro , Fu Linlin , Sugiyama Mariko , Takagi Hiroshi , Arima Hiroshi 
Published: October 2024

Disclosure: R. Banno: None. M. Kuno: None. L. Fu: None. M. Sugiyama: None. H. Takagi: None. H. Arima: None.

The brain system consisting of dopaminergic neurons (DNs) projecting primarily from the ventral tegmental area to the striatum plays a central role in the control of reward-based eating behavior and is referred to as the reward system. The neurocircuit of the reward system is activated by consuming palatable food such as a high-fat diet (HFD), processes information related to food reward, and provides emotional satiety. Multiple studies have reported that insulin and/or leptin receptor signaling in DNs or corticostriatal neurons (CSNs) can inhibit hedonic feeding behavior. Protein tyrosine phosphatase 1B (PTP1B) is a non-receptor tyrosine phosphatase that is widely expressed in the body and negatively regulates both insulin and leptin signaling pathways. Previous studies reported that PTP1B in the brain, especially the hypothalamus, regulates food intake, while the effect of PTP1B on feeding behavior in the reward system remains unclear. The present study aimed to examine whether PTP1B in DNs or CSNs affects feeding behavior. The DN or CSN-specific PTP1B deficient mice (D-KO or CS-KO) were generated by Cre-loxP system. First, to assess energy metabolism, HFD or a normal chow diet (NCD) was administered to wild-type mice (WT), D-KO and CS-KO after weaning, and their body weights were measured weekly. The adipose tissue weights of the HFD-fed group were measured at 20 weeks of age. Second, to assess glucose metabolism, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed on the NCD-fed group at 10 to 12 weeks of age. Third, to evaluate the rewarding value of HFD, the conditioned place preference (CPP) test was performed using the NCD-fed group at 12 to 14 weeks of age. Lastly, using the NCD-fed group at 19 to 21 weeks of age, the overeating of HFD was assessed with the binge-like eating model in which HFD was administered for the first 2 days, NCD for the next 5 days, and HFD again on the 8th day, and HFD intake during the first 60 minutes was measured. There were no significant differences in body weight, adipose tissue weight, GTT and ITT between WT and either D-KO or CS-KO, suggesting that PTP1B in DNs and CSNs did not affect the energy balance or glucose metabolism. On the other hand, while male and female WT mice exhibited a significant preference for HFD compared to NCD in the CPP test, both D-KO and CS-KO mice exhibited no preference for HFD. Furthermore, in the binge-like eating model, HFD intake for 60 minutes in WT amounted to more than 25% of the total daily calorie intake, indicating binge-like eating, but in female D-KO and S-KO, a significant decrease in HFD intake was observed compared to WT. In contrast to female mice, however, male D-KO and S-KO showed no significant differences in HFD intake for 60 minutes compared to WT. In summary, those data suggests that PTP1B in DNs and CSNs promote the rewarding value of HFD without affecting energy and glucose metabolism.

Presentation: 6/2/2024