Figure 2.

Effect of central TUG-905 administration on energy balance in obese mice. (A) TUG-905 chemical structure. (B) Schematic illustration of experimental timeline for TUG-905 daily bolus. TUG-905 (0.5 μg/μl) was injected by intracerebroventricular (ICV) administration once a day for 7 days. Body weight and food intake were measured daily. BAT temperature was measured at day 0 (the day before TUG-905 ICV treatment), day 4 and day 7 of the experiment. (C) Body weight change during the 7 days experimental period, (D) final body weight change after 7 days of TUG-905 ICV treatment (n = 20–24 mice/group), (E) daily food intake (n = 19–22 mice/group; 3 mice spilled food into the cage and feeding could not be recorded) and (F) circulating leptin levels (n = 6–9 mice/group) of vehicle and TUG-905 ICV-treated DIO mice. (g) Schematic illustration of the experimental strategy for continuous mini-pump TUG-905 ICV administration. Eight-week-old C57Bl/6J mice were fed with HFD for 8 consecutive weeks. Afterwards, these mice were submitted to an implantation of an osmotic minipump loaded with TUG-905 and transferred to the indirect calorimetry system for measurements after 7 days of surgery recovery. (H) Energy expenditure (EE) during dark and light phases, (I) cumulative EE, (J) ANCOVA analysis of EE using body weight as a covariate, (K) respiratory exchange ratio (RER) and (l) spontaneous locomotor activity (LA) (n = 5 mice/group) of vehicle and TUG-905 ICV-treated DIO mice. Data are expressed as MEAN ± SEM. Statistical significance was determined by two-way ANOVA (C and H), ANCOVA (J) or Student's t-test (D, E, F, I, K, and L); ∗P < 0.05 and ∗∗P < 0.01 vs. vehicle.