## 1 Introduction  
The hypothalamus is a regulator center involved in the integration of multiple factors and in the regulation of numerous homeostatic functions. Among them, the control of energy balance is one of the most complex hypothalamic tasks, as it also requires the coordinated participation of other brain regions and substances secreted by peripheral organs, such as the gastrointestinal tract or the adrenal glands. These peripheric signals send information to the central nervous system about the state of the energy stores, affecting the energy intake and expenditure [1, 2, 3]. For example, it was reported that gastric distension has a satiating effect [3]. In the control of food intake, a short-term regulation determines the beginning and the end of a meal; a long-term regulation helps to regulate the energy depots, and satiety regulates the interval between meals [3]. The balance between food intake and energy expenditure determines long-term energy homeostasis [1]. The regulation of feeding behavior is a complex mechanism exerted mainly by neuropeptides and neurotransmitters at the hypothalamic level, and the activity of certain hypothalamic neuronal groups sets the balance for maintaining proper homeostasis. In this regard, the activity of neurons located in the arcuate nucleus is particularly important. A group of neurons in this nucleus contain neuropeptide Y (NPY) and agouti-related peptide (AgRP) and are oexigenic, i.e., they promote food intake. These neurons are inhibitory for another population of neurons located in the arcuate nucleus that contain propoipomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), are anorexia, and inhibit feeding; see [4,5] for review. The interaction of both systems, POMC/CART and NPY/AgRP, is the basis for the regulation of energy homeostasis. These neuronal groups are under the influence of substances produced by the gastrointestinal tract, such as ghrelin, which activates NPY/AgRP neurons, and insulin or leptin, which activate POMC/CART neurons and inhibit NPY/AgRP neurons [1] (Figure 1). In addition, other hypothalamic regions and neuropeptides exert different effects on these neuronal groups [2] (Figure 2). In this regard, it was reported that orexins A and B, synthesized by neurons of the lateral hypothalamus, activate NPY/AgRP neurons located in the hypothalamic arcuate nucleus and that this projection is reciprocal [3,5]. Simultaneously, orexins inhibit POMC/CART neurons [1]. The oercismic effects of orexins are mainly mediated by NPY/AgRP neurons of the arcuate nucleus [2]. Orexins stimulate food intake and NPY expression (but not AgRP) in the arcuate nucleus when administered centrally, and their production is influenced by the nutritional state of the animal and respond to feeding status [1,2,6]; thus, the hypothalamic expression of the orexin precursor is increased during fasting [2,7,8]. Orexinergic neurons perceive rapidly the body's nutritional status and respond to metabolic signals, such as leptin and ghrelin levels or peripheral blood glucose, since orexin neurons are glucose-sensitive neurons excited by reduced blood glucose levels. Thus, orexin neurons can translate energy status into neural signals [1]; acting on this hypothalamic circuit, they can exert homeostatic regulation [8, 9, 10]. In addition, due to their extensive extrahypothalamic projections mainly to the limbic system, forebrain, and midbrain, orexins are involved in the regulation of complex behaviors that regulate food  
Figure 1: Schematic representation of the main hypothalamic regions implicated in the control of food intake. Neuroactive substances involved in feeding regulation are represented at the right side of the image, and receptors are represented at the left part of the schema.