A. Representative image of Vgat-IRES-Cre mouse expressing ChR2 neurons (green) in the LH. B. Behavioral protocol: Vgat-mice were fed an HFD or standard Chow diet for 12 weeks and were optostimulated in an open loop schedule. The mice had access to a sucrose solution (10%) in a sipper during the task. Mice had food and water ad libitum before the task. C-E. These six panels depict the cumulative licks (intake) during the open-loop task for lean versus obese mice administered with saline (C), tesofensine (Teso) 2 mg/kg (D), or 6 mg/kg (E) 30 minutes before the task. The left panels are control mice expressing EYFP, and the right panels express ChR2. Data are presented as mean ± SEM. The results show that compared to saline, tesofensine 2 mg/Kg reduced sucrose intake in lean mice expressing ChR2 (D right panel, see black line). In contrast, activating GABA neurons in obese mice significantly induced more sucrose intake than in lean mice.* p <0.05, Two-sample Kolmogorov-Smirnov test Lean vs. Obese. # p < 0.05 compared to its saline control group.