RESUMEN
Neuropeptide K (NPK) induces satiety in birds and mammals. We demonstrated that in birds this effect was associated with the hypothalamus, but beyond this little is known in any species regarding the central mechanism of action. Thus, this study was designed to identify hypothalamic molecular mechanisms associated with the food intake-inhibiting effects of NPK in chicks. In Experiment 1, intracerebroventricular (ICV) injection of 1.0 and 3.0â¯nmol of NPK reduced food intake and we identified an effective dose for microinjection. In Experiment 2, food intake was reduced when NPK was microinjected into the PVN. In Experiment 3, whole hypothalamus was collected from chicks at 1â¯h post-ICV NPK injection. The abundance of corticotropin-releasing factor (CRF) and agouti-related peptide (AgRP) mRNA was reduced in NPK-injected chicks. In Experiment 4, within the isolated paraventricular nucleus (PVN) there was less CRF mRNA, and within the arcuate nucleus (ARC) there was less AgRP mRNA, in NPK- than vehicle-treated chicks at 1â¯h post-injection. We conclude that there are first order neurons for NPK that reside within the PVN, and the anorexigenic effect of NPK is associated with a decrease in AgRP in the ARC.
Asunto(s)
Anorexia/tratamiento farmacológico , Depresores del Apetito/farmacología , Ingestión de Alimentos/genética , Taquicininas/farmacología , Proteína Relacionada con Agouti/genética , Animales , Anorexia/genética , Anorexia/patología , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/metabolismo , Pollos , Hormona Liberadora de Corticotropina/genética , Modelos Animales de Enfermedad , Ingestión de Líquidos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Infusiones Intraventriculares , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , ARN Mensajero/genética , Taquicininas/genéticaRESUMEN
LPLRFamide is a member of the RFamide peptide family that elicits an anorexigenic effect when centrally injected in chicks although the mechanism mediating this response is poorly understood. Therefore, the purpose of this experiment was to elucidate the hypothalamic mechanism of short-term anorexia after central administration of LPLRFamide in chicks. In Experiment 1 chicks centrally injected with LPLRFamide decreased food intake at 15min but not 30min following administration compared to vehicle-injected chicks. For Experiment 2, c-Fos immunoreactivity was quantified in several appetite-associated hypothalamic nuclei and in LPLRF-injected chicks, compared to vehicle-injected chicks, there was an increase in the number of reactive cells in the magnocellular division of the paraventricular nucleus. Lastly in Experiment 3, real time-PCR was performed and hypothalamic proopiomelanocortin (POMC) mRNA abundance was increased in LPRLFamide-injected chicks compared to vehicle-injected chicks. Thus, following central injection of LPLRFamide there is activation of the paraventricular nucleus of the hypothalamus and increased expression of hypothalamic POMC mRNA in chicks.