Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons

Isadora C. Furigo, Pryscila D. S. Teixeira, Gabriel O. Souza, Gisele C. L. Couto, Guadalupe García Romero, Mario Perelló, Renata Frazão, Lucila L. Elias, Martin Metzger, Edward O. List, John J. Kopchick and J. Donato ()
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Isadora C. Furigo: University of São Paulo
Pryscila D. S. Teixeira: University of São Paulo
Gabriel O. Souza: University of São Paulo
Gisele C. L. Couto: University of São Paulo
Guadalupe García Romero: University of São Paulo
Mario Perelló: Multidisciplinary Institute of Cell Biology
Renata Frazão: University of São Paulo
Lucila L. Elias: University of São Paulo
Martin Metzger: University of São Paulo
Edward O. List: Ohio University
John J. Kopchick: Ohio University
J. Donato: University of São Paulo

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08607-1

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