Re-introduction of MC4R into Kiss1 neurons in Kiss1Cre: Mc4rloxTB mice completely recovered estrous cyclicity, which was similar to controls (diestrus: p = 0.1932, proestrus: p = 0.8262, estrus: p = 0.0547, compared to controls; Figure 3E,Figure 2—figure supplement 1C, D) despite Kiss1Cre: Mc4rloxTB mice showing the same degree of obesity as Mc4rloxTB mice (Figure 3D), indicating that obesity per se was not mediating the irregular estrous cycles in Mc4r KO mice. This evidence concerns the gene KISS1 and Obesity.