(A and B) Body weight curve of male POMC-cre:PERKloxp/loxp and littermate control mice on a chow diet (A) or a 58% HFD (B). Statistical analyses were performed using 2-way repeated-measures ANOVA, with Bonferroni post hoc analyses applied. (C and D) Fat mass (C) and lean mass (D) of male POMC-cre:PERKloxp/loxp and littermate control mice on a 58% HFD at 20 weeks (A, n = 8–17 per group; B–D, n = 14–17 per group). (E) Male mice with PERK deficiency of POMC neurons displayed decreased food intake in both the 24-hour period and the dark cycle, while the food intake in the light cycle was unaffected. (F–J) Male POMC-cre:PERKloxp/loxp mice displayed decreased ambulatory activity in both light and dark cycles (F), while VO2 (G), VCO2 (H), respiratory exchange ratio (RER) (I), and heat production (J) remained unchanged in both the dark and light cycles. Black bars indicate littermate control mice. Red bars indicate POMC-cre:PERKloxp/loxp mice. (E–J) Data are from male mice (n = 5–7 per group) and are expressed as mean ± SEM. Unpaired t test, *P < 0.05, **P < 0.01.