El papel de la ghrelina en la señalizacion orexigenica mediada por la disponbilidad de glucosa

Abstract

Body weight maintenance and appetite depends on a central regulatory system through hypothalamic and extranypothalamic regions, as well as through peripheral control. The interplay between these two systems is mediated by neuronal connections, hormones, neuropeptides (NPY, agrp, orexin, MCH, pomc, cart, crh...) and nutrient derived signáis Çglucose avai 1 abi 1 ity). Ghreíin, a 28-acylated aminoàcid orexigenic peptide isolated from the stomach, is an endogenous "ligand of the secretagogue growth hormone receptor, which has been related to food intake and homeostasis. The aims of this study were to assess potential ghrelin interactions with glucose levels administering insulin and 2-deoxyglucose in appetite control and to identify potential mechanisms involving orexigenic/anorexigenic peripheral ghrelin mediated signáis by using a specific anti-ghrelin antibody (AGA). Employing immunohistochemistry techniques, we examined the c-fos expression in different hypothalamic areas and neurons. Peripheral blockade ghrelin significantly decreased food intake as induced from acute hypoglycemia (insulin) and glucopenia (2-DG). Also, the conjoint AGA and insulin or 2-DG administration produced an interactive effect of the glucostatic pathways involving the LH and VMH areas with the ghrelin signaling, specifically through orexin neurons. Furthermore, c-fos positive CRH neurons and CART expression increased in the PVN, implying that peripheral ghrelin plays an important role in reguiatory "glucostatic" feeding mechanisms due to its role as a "hunger" signal, which may contribute to energy homeostasis through both orexigenic/anorexigenic pathways. Finally, our results suggest that the NTS is a part of the ghrelin pathway that regulates the signalling cascade, which may be triggered by a drop in glucose levels.