Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons

Author(s):Show less -

Furigo, Isadora C. ^[1] ; Teixeira, Pryscila D. S. ^[1] ; de Souza, Gabriel O. ^[1] ; Couto, Gisele C. L. ^[1] ; Garcia Romero, Guadalupe ^{[1, 2]} ; Perello, Mario ^[2] ; Frazao, Renata ^[3] ; Elias, Lucila L. ^[4] ; Metzger, Martin ^[1] ; List, Edward O. ^{[5, 6]} ; Kopchick, John J. ^{[5, 6]} ; Donato, Jr., J. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Av Prof Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil

^[2] Multidisciplinary Inst Cell Biol, Lab Neurophysiol, Calle 526 & Camino Gen Belgrano, RA-1900 La Plata, BA - Argentina

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof Lineu Prestes 2415, BR-05508900 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Ohio Univ, Edison Biotechnol Inst, Konneker Res Ctr 206A, Athens, OH 45701 - USA

^[6] Ohio Univ, Heritage Coll Osteopath Med, Konneker Res Ctr 206A, Athens, OH 45701 - USA

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 10, FEB 8 2019.
• Web of Science Citations: 10

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. (AU)

• FAPESP's process: 16/09679-4 - Central effects of growth hormone on energetic metabolism and glicemic control
• Grantee: Isadora Clivatti Furigo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/16473-6 - Processing of aversive stimuli: circuitry between the laterodorsal tegmental nucleus, the habenula, and dorsal and median raphe nuclei
• Grantee: Martin Andreas Metzger
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/05007-4 - The effects of growth hormone on the ventromedial nucleus of the hypothalamus during food restriction
• Grantee: Gabriel Orefice de Souza
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/04006-4 - The importance of growth hormone's action on NPY/AgRP neurons
• Grantee: Gisele Cristina Lopes Couto Spiri
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/02983-2 - The role of growth hormone in the brain: relevance for neural functions and in disease
• Grantee: Jose Donato Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/21840-8 - Growth hormone signaling in the brain as a mediator of puberty and fertility
• Grantee: Renata Frazão
• Support Opportunities: Regular Research Grants