The mechanisms deputed to energetic control have been selected by ancestral diets resulting from the nutrient disposal during the evolution. Discovery of the leptin and its downstream peptidergic pathways has increased our understanding of the physiological system that regulate food intake in the last decade. Hypothalamus plays a key role in the regulation of the peripheral and central signals of energy requirements. Insulin and leptin, that reflect the adipose status, are able to long term influence these circuits. Gut hormones acutely modulated the pathways, resulting in a stimulation effects by ghreline, or in a inhibition effects by PYY and oxintomoduline. Moreover, brain centres signal energy homeostasis by monoamine release and endocannabinoid system. This review discusses the network of neuronal and hormonal signals, which contribute to the energetic control.