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

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)
17 Downloads (Pure)

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 languageEnglish
Article number662
Number of pages11
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 8 Feb 2019
Externally publishedYes

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

Fingerprint

Dive into the research topics of 'Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons'. Together they form a unique fingerprint.

Cite this