Artículo
GHSR controls food deprivation-induced activation of CRF neurons of the hypothalamic paraventricular nucleus in a LEAP2-dependent manner
Fernandez, Gimena
; Cabral, Agustina Soledad
; de Francesco, Pablo Nicolás
; Uriarte Donati, Maia
; Reynaldo, Mirta Beatriz; Castrogiovanni, Daniel Cayetano
; Zubiría, María Guillermina
; Giovambattista, Andres
; Cantel, Sonia; Deneulin, Severine; Fehrentz, Jean Alain; Tolle, Virginie; Schiöth, Helgi Birgir; Perello, Mario
Fecha de publicación:
04/2022
Editorial:
Springer
Revista:
Cellular and Molecular Life Sciences
ISSN:
1420-682X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Objective: Prolonged fasting is a major challenge for living organisms. An appropriate metabolic response to food deprivation requires the activation of the corticotropin-releasing factor-producing neurons of the hypothalamic paraventricular nucleus (PVHCRF neurons), which are a part of the hypothalamic–pituitary–adrenal axis (HPA), as well as the growth hormone secretagogue receptor (GHSR) signaling, whose activity is up- or down-regulated, respectively, by the hormones ghrelin and the liver-expressed antimicrobial peptide 2 (LEAP2). Since ghrelin treatment potently up-regulates the HPA axis, we studied the role of GHSR in mediating food deprivation-induced activation of the PVHCRF neurons in mice. Methods: We estimated the activation of the PVHCRF neurons, using immuno-staining against CRF and the marker of neuronal activation c-Fos in brain sections, and assessed plasma levels of corticosterone and glucose in different pharmacologically or genetically manipulated mouse models exposed, or not, to a 2-day food deprivation protocol. In particular, we investigated ad libitum fed or food-deprived male mice that: (1) lacked GHSR gene expression, (2) had genetic deletion of the ghrelin gene, (3) displayed neurotoxic ablation of the hypothalamic arcuate nucleus, (4) were centrally treated with an anti-ghrelin antibody to block central ghrelin action, (5) were centrally treated with a GHSR ligand that blocks ghrelin-evoked and constitutive GHSR activities, or (6) received a continuous systemic infusion of LEAP2(1–12). Results: We found that food deprivation results in the activation of the PVHCRF neurons and in a rise of the ghrelin/LEAP2 molar ratio. Food deprivation-induced activation of PVHCRF neurons required the presence and the signaling of GHSR at hypothalamic level, but not of ghrelin. Finally, we found that preventing the food deprivation-induced fall of LEAP2 reverses the activation of the PVHCRF neurons in food-deprived mice, although it has no effect on body weight or blood glucose. Conclusion: Food deprivation-induced activation of the PVHCRF neurons involves ghrelin-independent actions of GHSR at hypothalamic level and requires a decrease of plasma LEAP2 levels. We propose that the up-regulation of the actions of GHSR associated to the fall of plasma LEAP2 level are physiologically relevant neuroendocrine signals during a prolonged fasting.
Palabras clave:
CONSTITUTIVE GHSR ACTIVITY
,
CRH NEURONS
,
GHRELIN
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Colecciones
Articulos(IMBICE)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA CELULAR (I)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA CELULAR (I)
Citación
Fernandez, Gimena; Cabral, Agustina Soledad; de Francesco, Pablo Nicolás; Uriarte Donati, Maia; Reynaldo, Mirta Beatriz; et al.; GHSR controls food deprivation-induced activation of CRF neurons of the hypothalamic paraventricular nucleus in a LEAP2-dependent manner; Springer; Cellular and Molecular Life Sciences; 79; 5; 4-2022; 1-18
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