CRTC1 and obesity due to melanocortin 4 receptor deficiency: Gender difference in the homeostatic regulation of energy balance. Crtc1–/– males are hyperphagic and rapidly develop obesity on normal chow diet. Crtc1–/– females exhibit mild late-onset obesity without hyperphagia.Alterations in the expression of several orexigenic and anorexigenic hypothalamic genes in mutant males.Crtc1–/– males’ hyperphagic behavior is restricted to the diurnal (resting) phase of the light cycle during which they have a higher locomotor activity.