Role of Orexin system in obesity

Obesity is a public health disease and its incidence is steadily increasing both in adults and in children especially in the Western World. It is important to understand the underlying mechanisms of obesity and possible treatments as the orexin system with its receptors, which are involved in different physiological processes. In fact, the aim of this mini-review is to consider the importance of the orexin system and the role that orexin plays in the regulation of obesity and physical activity. Furthermore to demonstrate how the orexin and its receptors fit within a network distributed in multiple brain areas, each with specific actions, whose activation and interconnection has been seen to lead to a lower propensity for increase of fat mass, it could thus constitute an important future target for prevention and treatment of obesity. Figure 1: Composition of Orexin-A and Orexin-B. OX1R: orexin receptor type1. OX2R: orexin receptor type-2. Bi olo gy a nd Micine ISSN: 0974-8369 Biology and Medicine Citation: Messina G, Monda V, Moscatelli F, Valenzano AA, Monda G, et al. (2015) Role of Orexin system in obesity. Biol Med (Aligarh) 7: 248. doi: 10.4172/0974-8369.1000248 Volume 7 • Issue 4 • 1000248 Biol Med (Aligarh) ISSN: 0974-8369 BLM, an open access journal Page 2 of 6 Over the location in the lateral hypothalamus, which were initially described, the orexin and its receptors have been highlighted in neuronal bodies and positive fibers present in different regions of the central nervous system (CNS) and their position is in connection with the functions performed. Therefore a lot of brain sites join in this regulatory network through a significant number of neurotransmitters (Figure 3). The functions of the orexin system are expressed in different brain regions, they control the same behaviors; in fact many of the brain sites that participate in the SPA network also participate in regulatory networks for food intake and other aspects of energy balance. Several brain regions receive orexinergic input and express the OXR and this instance suggests that the behavioral outcomes of the orexin system are due to simultaneous activation of the OXR in different brain regions connected through projections. Orexins are produced in a particular area of the hypothalamus, including the caudal lateral hypothalamus and adjacent perifornical area [12] and, from these sites, orexin projects throughout the other areas of the brain. On the basis of anatomical predisposition appears to be valid the hypothesis that the effects of the action of the orexin system derive from a series of parallel signals that come from different brain regions [13]. It is important to know that orexin neurons are in a baseline intrinsic state of depolarized activity [14] and are highly influenced by local conditions in an intralateral hypothalamic local network [15]. The Activation of the OXR causes depolarization and active neuronal firing by four possible mechanisms: • activation of non-specific cationic currents • activation of the Na+/Ca2+ exchanger • phosphorylation-dependent inhibition of inwardly rectifying K+ channels • increase in Ca2+ through activation of Land N-type Ca2+channels [16–20]. The type of mechanism appears to be cell-dependent and both orexin subtypes can couple to many Gproteins that cause neuronal depolarization through many mechanisms cell-specific (Figure 4). The Role Of Orexin In Brown Adipose Tissue Thermogenesis And Activation Of Sympathetic Nervous System Orexin system also influences body temperature. In fact, an Intracerebroventricular (icv) administration of orexin system induces an increase in the firing rate of the sympathetic nerves to interscapular brown adipose tissue (IBAT), accompanied with a rise in IBAT and colonic temperatures [21]. In addition, the presence of orexin receptors in many cerebral areas suggests that additional functions are played by orexin system [22]. In general, those experiments demonstrate that an icv injection of orexin system increases the temperature of IBAT, which is the most important effect or of non shivering thermogenesis in the rat [23], illustrating that the rise in heat production is also due to the activation of thermogenesis unrelated to muscle activity. IBAT activity is controlled by the sympathetic nervous system, and factors, which influence thermogenesis, appear to act centrally to modify the sympathetic outflow to IBAT [24]. The increase in colonic temperature emphasizes the effect of orexin system on the “core” temperature confirming the inclusion of orexin system among the peptides controlling body temperature. The rise of the sympathetic discharge induced by orexin system is corroborated by the increase in heart rate, although a possible reduction on the vagal tone cannot be excluded. Since Van Den Pol [25] demonstrated a direct innervation of the intermedio lateral column of spinal cord by orexin-fibers, there might be another direct pathway of the orexin induced activation of the sympathetic nervous system. Materials and Methods