Methods and therapeutics are provided for treating metabolic disorders by activation of melanocortin signaling pathways. Generally, the methods and therapeutics can induce activation of melanocortin receptor signaling to increase energy expenditure and induce weight loss. In one embodiment, a method for performing a diagnostic procedure can be chosen, energy expenditure then assess in light of the diagnostic procedure and a definitive procedure(s) can be selected dependent on the outcome of the energy assessment. In another embodiment, a diagnostic procedure can be chosen to activate melanocortin receptor pathways, energy expenditure can be assessed and a definitive procedure(s) can be chosen that selectively and optimally activate melanocortin receptor pathways.