Deletion of growth hormone receptor in hypothalamic neurons affects the adaptation capacity to aerobic exercise

Autor(es)

Pedroso, Joao A. B. ^[1] ; dos Santos, Lucas B. P. ^[1] ; Furigo, Isadora C. ^[1] ; Spagnol, Alexandre R. ^[2] ; Wasinski, Frederick ^[1] ; List, Edward O. ^{[3, 4]} ; Kopchick, John J. ^{[3, 4]} ; Donato Jr, Jose

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508000 Sao Paulo - Brazil

^[3] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 - USA

^[4] Ohio Univ, Heritage Coll Osteopath Med, Athens, OH 45701 - USA

• Tipo de documento: Artigo Científico
• Fonte: Peptides; v. 135, JAN 2021.
• Citações Web of Science: 1

Resumo

The hypothalamus mediates important exercise-induced metabolic adaptations, possibly via hormonal signals. Hypothalamic leptin receptor (LepR)and steroidogenic factor 1 (SF1)-expressing neurons are directly responsive to growth hormone (GH) and deletion of GH receptor (GHR) in these cells impairs neuroendocrine responses during situations of metabolic stress. In the present study, we determined whether GHR ablation in LepRor SF1-expressing cells modifies acute and chronic metabolic adaptations to exercise. Male mice carrying deletion of GHR in LepRor SF1-expressing cells were submitted to 8 weeks of treadmill running training. Changes in aerobic performance and exercise-induced metabolic adaptations were determined. Mice carrying GHR deletion in LepR cells showed increased aerobic performance after 8 weeks of treadmill training, whereas GHR ablation in SF1 cells prevented improvement in running capacity. Trained mice carrying GHR ablation in SF1 cells exhibited increased fat mass and reduced cross-sectional area of the gastrocnemius muscle. In contrast, deletion of GHR in LepR cells reduced fat mass and increased gastrocnemius muscle hypertrophy, energy expenditure and voluntary locomotor activity in trained mice. Although glucose tolerance was not significantly affected by targeted deletions, glycemia before and immediately after maximum running tests was altered by GHR ablation. In conclusion, GHR signaling in hypothalamic neurons regulates the adaptation capacity to aerobic exercise in a cell-specific manner. These findings suggest that GH may represent a hormonal cue that informs specific hypothalamic neurons to produce exercise-induced acute and chronic metabolic adaptations. (AU)

• Processo FAPESP: 16/20897-3 - Papel dos neurônios orexina como mediadores dos efeitos centrais induzidos pelo hormônio do crescimento
• Beneficiário: Frederick Wasinski
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/02983-2 - Ação do hormônio do crescimento no sistema nervoso: relevância para as funções neurais e na doença
• Beneficiário: Jose Donato Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/09679-4 - Estudo dos efeitos centrais do hormônio do crescimento sobre o metabolismo energético e controle glicêmico
• Beneficiário: Isadora Clivatti Furigo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado