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Obesity is one of the most relevant public health concerns today and it is now evident that body weight control is achieved through highly integrated physiological interactions like nutrient selection as well as being influenced by genetic and environmental factors. Moreover, energy balance regulation is a complex process aimed at maintaining constant energy stores. Presenting a detailed and comprehensive account of the roles of specific peptides in energy balance, food intake control and co-morbidities, this review provides a better understanding of the patho-physiology of energy balance and obesity.