IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
artículos
Título:
Divergent Neuronal Circuitries Underlying Acute Orexigenic Effects of Peripheral or Central Ghrelin: Critical Role of Brain Accessibility
Autor/es:
A. CABRAL; S.VALDIVIA; G.FERNANDEZ; M. REYNALDO; M. PERELLÓ
Revista:
JOURNAL OF NEUROENDOCRINOLOGY.
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2014 p. 1 - 13
ISSN:
0953-8194
Resumen:
Ghrelin is an octanoylated peptide hormone that potently and rapidly increases food intake. The
orexigenic action of ghrelin involves the hypothalamic arcuate nucleus (ARC), which is accessible
to plasma ghrelin and expresses high levels of the ghrelin receptor. Local administration of ghrelin
in a variety of other brain nuclei also increases food intake. It is currently unclear, however,
whether these non-ARC ghrelin brain targets are impacted by physiological increases of plasma
ghrelin. Thus, the present study aimed to clarify which ghrelin brain targets participate in the
short-term orexigenic actions of ghrelin. First, c-Fos induction into mouse brains centrally or
peripherally treated with ghrelin was analysed. It was confirmed that peripherally administered
ghrelin dose-dependently increases food intake and mainly activates c-Fos in ARC neurones. By
contrast, centrally administered ghrelin activates c-Fos in a larger number of brain nuclei. To
determine which nuclei are directly accessible to ghrelin, mice were centrally or peripherally
injected with a fluorescent ghrelin tracer. It was found that peripherally injected tracer mainly
accesses the ARC, whereas centrally injected tracer reaches most brain areas known to express
ghrelin receptors. Subsequently, the effects of ghrelin were tested in ARC-ablated mice and it
was found that these mice failed to increase food intake in response to peripherally administered
ghrelin but fully responded to centrally administered ghrelin. ARC-ablated mice showed patterns
of ghrelin-induced c-Fos expression similar to those seen in control mice with the exception
of the ARC, where no c-Fos was found. Thus, peripheral ghrelin mainly accesses the ARC, which
is required for the orexigenic effects of the hormone. Central ghrelin accesses a variety of
nuclei, which can mediate the orexigenic effects of the hormone, even in the absence of an
intact ARC.