Cholinergic neurons in the hypothalamus and dorsal motor nucleus of the vagus are directly responsive to growth hormone

Autor(es)

Quaresma, Paula G. F. ^[1] ; Teixeira, Pryscila D. S. ^[1] ; Wasinski, Frederick ^[1] ; Campos, Ana M. P. ^[1] ; List, Edward O. ^[2] ; Kopchick, John J. ^[2] ; Donato, Jr., Jose ^[1]

Afiliação do(s) autor(es)

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

^[2] Ohio Univ, Heritage Coll Osteopath Med, Edison Biotechnol Inst, Athens, OH 45701 - USA

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 259, OCT 15 2020.
• Citações Web of Science: 0

Resumo

Aims: Cholinergic neurons are distributed in brain areas containing growth hormone (GH)-responsive cells. We determined if cholinergic neurons are directly responsive to GH and the metabolic consequences of deleting the GH receptor (GHR) specifically in choline acetyltransferase (ChAT)-expressing cells. Main methods: Mice received an acute injection of GH to detect neurons co-expressing ChAT and phosphorylated STAT5 (pSTAT5), a well-established marker of GH-responsive cells. For the physiological studies, mice carrying ablation of GHR exclusively in ChAT-expressing cells were produced and possible changes in energy and glucose homeostasis were determined when consuming regular chow or high-fat diet (HFD). Key findings: The majority of cholinergic neurons in the arcuate nucleus (60%) and dorsomedial nucleus (84%) of the hypothalamus are directly responsive to GH. Approximately 34% of pre-ganglionic parasympathetic neurons in the dorsal motor nucleus of the vagus also exhibited GH-induced pSTAT5. GH-induced pSTAT5 in these ChAT neurons was absent in GHR ChAT knockout mice. Mice carrying ChAT-specific GHR deletion, either in chow or HFD, did not exhibit significant changes in body weight, body adiposity, lean body mass, food intake, energy expenditure, respiratory quotient, ambulatory activity, serum leptin levels, glucose tolerance, insulin sensitivity and metabolic responses to 2-deoxy-D-glucose. However, GHR deletion in ChAT neurons caused decreased hypothalamic Pomc mRNA levels in HFD mice. Significance: Cholinergic neurons that regulate the metabolism are directly responsive to GH, although GHR signaling in these cells is not required for energy and glucose homeostasis. Thus, the physiological importance of GH action on cholinergic neurons still needs to be identified. (AU)

• 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: 17/25281-3 - Efeitos do hormônio do crescimento sobre os neurônios POMC, colinérgicos e do núcleo paraventricular do hipotálamo: implicações no controle do metabolismo energético e glicêmico
• Beneficiário: Paula Gabriele Fernandes Quaresma Bergonsi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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