Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons

Isadora C Furigo; Pryscila D S Teixeira; Gabriel O de Souza; Gisele C L Couto; Guadalupe García Romero; Mario Perelló; Renata Frazão; Lucila L Elias; Martin Metzger; Edward O List; John J Kopchick; J Donato

doi:10.1038/s41467-019-08607-1

Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons

Isadora C Furigo, Pryscila D S Teixeira, Gabriel O de Souza, Gisele C L Couto, Guadalupe García Romero, Mario Perelló, Renata Frazão, Lucila L Elias, Martin Metzger, Edward O List, John J Kopchick, J Donato

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Abstract

Weight loss triggers important metabolic responses to conserve energy, especially via the fall in leptin levels. Consequently, weight loss becomes increasingly difficult with weight regain commonly occurring in most dieters. Here we show that central growth hormone (GH) signaling also promotes neuroendocrine adaptations during food deprivation. GH activates agouti-related protein (AgRP) neurons and GH receptor (GHR) ablation in AgRP cells mitigates highly characteristic hypothalamic and metabolic adaptations induced by weight loss. Thus, the capacity of mice carrying an AgRP-specific GHR ablation to save energy during food deprivation is impaired, leading to increased fat loss. Additionally, administration of a clinically available GHR antagonist (pegvisomant) attenuates the fall of whole-body energy expenditure of food-deprived mice, similarly as seen by leptin treatment. Our findings indicate GH as a starvation signal that alerts the brain about energy deficiency, triggering key adaptive responses to conserve limited fuel stores.

Original language	English
Article number	662
Number of pages	11
Journal	Nature Communications
Volume	10
DOIs	https://doi.org/10.1038/s41467-019-08607-1
Publication status	Published - 8 Feb 2019
Externally published	Yes

Bibliographical note

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons
license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in
a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Keywords

Agouti-Related Protein/genetics
Animals
Body Weight/drug effects
Brain/drug effects
Energy Metabolism/drug effects
Female
Growth Hormone/metabolism
Human Growth Hormone/analogs & derivatives
Leptin/metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Somatotropin/genetics
Weight Loss/drug effects

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10.1038/s41467-019-08607-1Licence: CC BY

PublishedFinal published version, 2.09 MBLicence: CC BY

Cite this

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title = "Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons",

abstract = "Weight loss triggers important metabolic responses to conserve energy, especially via the fall in leptin levels. Consequently, weight loss becomes increasingly difficult with weight regain commonly occurring in most dieters. Here we show that central growth hormone (GH) signaling also promotes neuroendocrine adaptations during food deprivation. GH activates agouti-related protein (AgRP) neurons and GH receptor (GHR) ablation in AgRP cells mitigates highly characteristic hypothalamic and metabolic adaptations induced by weight loss. Thus, the capacity of mice carrying an AgRP-specific GHR ablation to save energy during food deprivation is impaired, leading to increased fat loss. Additionally, administration of a clinically available GHR antagonist (pegvisomant) attenuates the fall of whole-body energy expenditure of food-deprived mice, similarly as seen by leptin treatment. Our findings indicate GH as a starvation signal that alerts the brain about energy deficiency, triggering key adaptive responses to conserve limited fuel stores.",

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AU - Romero, Guadalupe García

AU - Perelló, Mario

AU - Frazão, Renata

AU - Elias, Lucila L

AU - Metzger, Martin

AU - List, Edward O

AU - Kopchick, John J

AU - Donato, J

N1 - Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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N2 - Weight loss triggers important metabolic responses to conserve energy, especially via the fall in leptin levels. Consequently, weight loss becomes increasingly difficult with weight regain commonly occurring in most dieters. Here we show that central growth hormone (GH) signaling also promotes neuroendocrine adaptations during food deprivation. GH activates agouti-related protein (AgRP) neurons and GH receptor (GHR) ablation in AgRP cells mitigates highly characteristic hypothalamic and metabolic adaptations induced by weight loss. Thus, the capacity of mice carrying an AgRP-specific GHR ablation to save energy during food deprivation is impaired, leading to increased fat loss. Additionally, administration of a clinically available GHR antagonist (pegvisomant) attenuates the fall of whole-body energy expenditure of food-deprived mice, similarly as seen by leptin treatment. Our findings indicate GH as a starvation signal that alerts the brain about energy deficiency, triggering key adaptive responses to conserve limited fuel stores.

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JO - Nature Communications

JF - Nature Communications

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ER -

Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons

Abstract

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Keywords

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