Taken together, results from the literature as well as in-house studies of CART knockout models generally support the property of CART as a satiety factor and an anorexigenic signal in the brain, as evident in the elevation in body weight gain attributable mostly to the increased fat mass consistent across studies, although controversy exists for the corresponding food intake data. As for the aspect of energy intake, RER was demonstrated to be reduced both under the conditions of CART overexpression and ablation, suggesting fat was metabolized as the primary fuel for energy supply. A possible reason could be that although CART may intrinsically promote the utilization of fat as the predominant fuel source for reducing energy intake, the effectiveness of CART deletion on the disturbance of lipid metabolism hence accumulation of adiposity may have surmounted the simultaneous CART deficiency-induced enhancement of energy intake, resulting in a net reduction in RER based on the readily available fat depots.