Impact of intra-GC Ex-4 in context of a chronic high-fat diet. A, Weekly elevations in body weight of mice on the LF or HF diet during the development of weight gain over 6 weeks. B, Weekly elevations in body weight from A, divided by sex. C, Comparing the average change in body weight on the sixth week of HF maintenance in males and females; ***p < 0.001 males versus females. D, Intake (kcal/body weight) of HF by the HF-maintained group, 2 h into the dark cycle following intra-GC Ex-4 (left) or the same when LF group was monitored for LF intake (right). E, Schematic of experimental timeline, cohort of animals on HF acutely switched to LF (top), or cohort of animals on LF acutely switched to HF (bottom). F, Left, LF food intake (kcal/body weight) of the HF-maintained group, 2 h into the dark cycle following intra-CG Ex-4 infusion; *p < 0.05, ***p < 0.001 versus 0 µg Ex-4. Right, HF food intake (kcal/body weight) of the LF-maintained group, 2 h into the dark cycle following intra-GC Ex-4; *p < 0.05 0.3 versus 0 µg Ex-4. G, Visceral fat (g) calculated over body weight (g) at the end of the experiment (see above, Materials and Methods); ***p < 0.005 HF males versus HF females. H, Representative cannula infusion tip placements of mice included in D, F, and G; n = 13–22 mice/diet condition.