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AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin

GH (growth hormone) secretion/action is modulated by alterations in energy homeostasis, such as malnutrition and obesity. Recent data have uncovered the mechanism by which hypothalamic neurons sense nutrient bioavailability, with a relevant contribution of AMPK (AMP-activated protein kinase) and mTO...

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Autores principales: Vázquez, María J., Novelle, Marta G., Rodríguez-Pacheco, Francisca, Lage, Ricardo, Varela, Luis, López, Miguel, Pinilla, Leonor, Tena-Sempere, Manuel, Diéguez, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564832/
https://www.ncbi.nlm.nih.gov/pubmed/32839401
http://dx.doi.org/10.3390/cells9091940
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author Vázquez, María J.
Novelle, Marta G.
Rodríguez-Pacheco, Francisca
Lage, Ricardo
Varela, Luis
López, Miguel
Pinilla, Leonor
Tena-Sempere, Manuel
Diéguez, Carlos
author_facet Vázquez, María J.
Novelle, Marta G.
Rodríguez-Pacheco, Francisca
Lage, Ricardo
Varela, Luis
López, Miguel
Pinilla, Leonor
Tena-Sempere, Manuel
Diéguez, Carlos
author_sort Vázquez, María J.
collection PubMed
description GH (growth hormone) secretion/action is modulated by alterations in energy homeostasis, such as malnutrition and obesity. Recent data have uncovered the mechanism by which hypothalamic neurons sense nutrient bioavailability, with a relevant contribution of AMPK (AMP-activated protein kinase) and mTOR (mammalian Target of Rapamycin), as sensors of cellular energy status. However, whether central AMPK-mediated lipid signaling and mTOR participate in the regulation of pituitary GH secretion remains unexplored. We provide herein evidence for the involvement of hypothalamic AMPK signaling, but not hypothalamic lipid metabolism or CPT-1 (carnitine palmitoyltransferase I) activity, in the regulation of GH stimulatory responses to the two major elicitors of GH release in vivo, namely GHRH (growth hormone–releasing hormone) and ghrelin. This effect appeared to be GH-specific, as blocking of hypothalamic AMPK failed to influence GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) secretion. Additionally, central mTOR inactivation did not alter GH responses to GHRH or ghrelin, nor this blockade affected LH responses to GnRH in vivo. In sum, we document here for the first time the indispensable and specific role of preserved central AMPK, but not mTOR, signaling, through a non-canonical lipid signaling pathway, for proper GH responses to GHRH and ghrelin in vivo.
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spelling pubmed-75648322020-10-26 AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin Vázquez, María J. Novelle, Marta G. Rodríguez-Pacheco, Francisca Lage, Ricardo Varela, Luis López, Miguel Pinilla, Leonor Tena-Sempere, Manuel Diéguez, Carlos Cells Article GH (growth hormone) secretion/action is modulated by alterations in energy homeostasis, such as malnutrition and obesity. Recent data have uncovered the mechanism by which hypothalamic neurons sense nutrient bioavailability, with a relevant contribution of AMPK (AMP-activated protein kinase) and mTOR (mammalian Target of Rapamycin), as sensors of cellular energy status. However, whether central AMPK-mediated lipid signaling and mTOR participate in the regulation of pituitary GH secretion remains unexplored. We provide herein evidence for the involvement of hypothalamic AMPK signaling, but not hypothalamic lipid metabolism or CPT-1 (carnitine palmitoyltransferase I) activity, in the regulation of GH stimulatory responses to the two major elicitors of GH release in vivo, namely GHRH (growth hormone–releasing hormone) and ghrelin. This effect appeared to be GH-specific, as blocking of hypothalamic AMPK failed to influence GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) secretion. Additionally, central mTOR inactivation did not alter GH responses to GHRH or ghrelin, nor this blockade affected LH responses to GnRH in vivo. In sum, we document here for the first time the indispensable and specific role of preserved central AMPK, but not mTOR, signaling, through a non-canonical lipid signaling pathway, for proper GH responses to GHRH and ghrelin in vivo. MDPI 2020-08-21 /pmc/articles/PMC7564832/ /pubmed/32839401 http://dx.doi.org/10.3390/cells9091940 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vázquez, María J.
Novelle, Marta G.
Rodríguez-Pacheco, Francisca
Lage, Ricardo
Varela, Luis
López, Miguel
Pinilla, Leonor
Tena-Sempere, Manuel
Diéguez, Carlos
AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin
title AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin
title_full AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin
title_fullStr AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin
title_full_unstemmed AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin
title_short AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin
title_sort ampk-dependent mechanisms but not hypothalamic lipid signaling mediates gh-secretory responses to ghrh and ghrelin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564832/
https://www.ncbi.nlm.nih.gov/pubmed/32839401
http://dx.doi.org/10.3390/cells9091940
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