Although the effective participation of CRTC1 in the entrainment of circadian clock in vivo and the consequent effect on the circadian energy homeostasis are not completely understood, the behavioral observation of Crtc1–/– mice suggested that the obesity of mutant males is due to overeating during the resting phase of the light cycle and to circadian alteration of spontaneous locomotor activity (Rossetti et al., 2017). Here, CLOCK is linked to obesity due to melanocortin 4 receptor deficiency.