Neonatal Ex-4 protects adult female mice from diet-induced obesity through enhanced energy expenditure. (A–E) After neonatal vehicle or Ex-4 administration, mice were weaned onto a 10% LFD or 45% HFD. Body weight of male (A) and female (B) mice monitored for 42 weeks. Data expressed as mean ± SEM; n = 10–15 mice/group. *, p < 0.05, relative to corresponding vehicle. (C–E) Mice sacrificed at postnatal week 42 for dissection of male (C) and female (D) inguinal and perigonadal fat depots. Tissue weights normalized to body weight and data represented as means ± SEM; n = 3–9 mice/group. *, p < 0.05 relative to vehicle LFD, #, p < 0.05 relative to vehicle HFD. (E) NMR analysis of 42 week old females. Values represented as means ± SEM; n = 4 mice/group. *, p < 0.05 relative to vehicle LFD, #, p < 0.05 relative to vehicle HFD (Two-tailed Student's t test). (F–H) Indirect calorimetry performed on 42 week old female mice. Oxygen consumption (F–G) shown over 24 h period (F) or as a 24 h average (G). Energy expenditure shown as a 24 h average. All raw values normalized to lean mass. Data expressed as mean ± SEM; n = 4–8 mice/group. *, p < 0.05, relative to corresponding vehicle LFD, #, p < 0.05 relative to vehicle HFD. (Two-way ANOVA with Tukey Posthoc test).