RESUMEN
Hypothalamic pro-opiomelanocortin (POMC) neurons help regulate long-term energy stores. POMC neurons are also found in the nucleus tractus solitarius (NTS), a region regulating satiety. We show here that mouse brainstem NTS POMC neurons are activated by cholecystokinin (CCK) and feeding-induced satiety and that activation of the neuronal melanocortin-4 receptor (MC4-R) is required for CCK-induced suppression of feeding; the melanocortin system thus provides a potential substrate for integration of long-term adipostatic and short-term satiety signals.
Asunto(s)
Ingestión de Alimentos/fisiología , Hipotálamo/metabolismo , Receptor de Melanocortina Tipo 4/metabolismo , Respuesta de Saciedad/fisiología , Sincalida/análogos & derivados , Sincalida/fisiología , Núcleo Solitario/metabolismo , Animales , Núcleo Arqueado del Hipotálamo/citología , Núcleo Arqueado del Hipotálamo/metabolismo , Regulación hacia Abajo , Metabolismo Energético/fisiología , Conducta Alimentaria/fisiología , Femenino , Hipotálamo/citología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Vías Nerviosas/citología , Vías Nerviosas/metabolismo , Neuronas/metabolismo , Proopiomelanocortina/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor de Melanocortina Tipo 4/deficiencia , Núcleo Solitario/citologíaRESUMEN
The central melanocortin system plays a critical role in regulation of energy balance, including thermogenesis in brown adipose tissue (BAT). Activation of the hypothalamic melanocortin signaling stimulates sympathetically-mediated interscapular BAT (IBAT) thermogenesis. The rostral raphe pallidus (rRPa) and adjacent area have been proposed as the location of sympathetic premotor neurons for the central nervous system (CNS) control of IBAT thermogenesis. To determine if neuronal activity in rRPa area is required for the central melanocortin-induced thermogenesis, we studied the effects of inhibition of the activity of neurons in the rRPa area on the sympathetic nerve activity (SNA) to IBAT evoked by lateral ventricular injection of the melanocortin 3/4 receptor (MC3/4R) agonist, MTII, in urethane-chloralose-anesthetized rats and the effects on O(2) consumption induced by third or fourth ventricular injection of MTII in conscious freely moving mice. Icv injection of MTII (1 nmol) significantly increased rat IBAT SNA (+741% of control). Both third and fourth ventricular injections of MTII (1 nmol) significantly increased O(2) consumption in conscious C57BL/6J mice (45% higher than that of saline control for third ventricular injection and 44% higher than that of saline control for fourth ventricular injection). The increases in IBAT SNA and in O(2) consumption were reversed by inhibition of neurons in the rRPa and adjacent area with microinjections of glycine or muscimol into rRPa. These results suggest that the neurons in the RPa and its immediate vicinity play an essential role in mediating the increase in IBAT thermogenesis induced by activation of central melanocortin signaling.