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

Authors :
María J. Vázquez
Marta G. Novelle
Francisca Rodríguez-Pacheco
Ricardo Lage
Luis Varela
Miguel López
Leonor Pinilla
Manuel Tena-Sempere
Carlos Diéguez
Source :
Cells, Vol 9, Iss 9, p 1940 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

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.

Details

Language :
English
ISSN :
20734409
Volume :
9
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.8c02a2d0ed9448cda5dfcb5bb7a78a65
Document Type :
article
Full Text :
https://doi.org/10.3390/cells9091940