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Nat Commun. 2019 Feb 8;10(1):662. doi: 10.1038/s41467-019-08607-1.

Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons.

Author information

1
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil.
2
Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology, Calle 526 y Camino General Belgrano, La Plata, BA, 1900, Argentina.
3
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 2415, São Paulo, SP, 05508-900, Brazil.
4
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil.
5
Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Konneker Research Center 206A, Athens, OH, 45701, USA.
6
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil. jdonato@icb.usp.br.

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.

PMID:
30737388
PMCID:
PMC6368581
DOI:
10.1038/s41467-019-08607-1
[Indexed for MEDLINE]
Free PMC Article

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