Compared to vehicle microinjection, intra‐VMH microinjection of the mixed melanocortin receptor agonist MTII significantly increased (A) EE, (B) and (D) physical activity levels, and also (C) decreased the RER, implicating increased lipid oxidation. When activity levels and workload were equalized using a treadmill walking protocol, the ability of MTII to (E) elevate EE, (F) increase and (G) lower RER remained, indicating decreased locomotor efficiency. *Significantly different from vehicle, P < 0.05 (n = 10).