دورية أكاديمية
GHSR in a Subset of GABA Neurons Controls Food Deprivation-Induced Hyperphagia in Male Mice.
| العنوان: | GHSR in a Subset of GABA Neurons Controls Food Deprivation-Induced Hyperphagia in Male Mice. |
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| المؤلفون: | Cornejo MP; Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina., Fernandez G; Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina., Cabral A; Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina., Barrile F; Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina., Heredia F; Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina., García Romero G; Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina., Zubimendi Sampieri JP; YPF Tecnología-CONICET, Berisso 1923, Buenos Aires, Argentina., Quelas JI; YPF Tecnología-CONICET, Berisso 1923, Buenos Aires, Argentina., Cantel S; Institut des Biomolécules Max Mousseron, Univ Montpellier, CNRS, ENSCM, Montpellier, France., Fehrentz JA; Institut des Biomolécules Max Mousseron, Univ Montpellier, CNRS, ENSCM, Montpellier, France., Alonso A; Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia 30100, Spain.; Institute of Biomedical Research of Murcia-IMIB, Virgen de la Arrixaca University Hospital, Murcia 30100, Spain., Pla R; Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia 30100, Spain.; Institute of Biomedical Research of Murcia-IMIB, Virgen de la Arrixaca University Hospital, Murcia 30100, Spain., Ferran JL; Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia 30100, Spain.; Institute of Biomedical Research of Murcia-IMIB, Virgen de la Arrixaca University Hospital, Murcia 30100, Spain., Andreoli MF; Instituto de Desarrollo e Investigaciones Pediátricas (IDIP), HIAEP Sor María Ludovica de La Plata, Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina.; Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala 751 24, Sweden., De Francesco PN; Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina., Perelló M; Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE), Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata 1900, Buenos Aires, Argentina.; Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala 751 24, Sweden. |
| المصدر: | Endocrinology [Endocrinology] 2024 May 27; Vol. 165 (7). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375040 Publication Model: Print Cited Medium: Internet ISSN: 1945-7170 (Electronic) Linking ISSN: 00137227 NLM ISO Abbreviation: Endocrinology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Los Angeles, Calif. : Association for the Study of Internal Secretions, |
| مواضيع طبية MeSH: | GABAergic Neurons*/metabolism , Receptors, Ghrelin*/genetics , Receptors, Ghrelin*/metabolism , Hyperphagia*/metabolism , Ghrelin*/metabolism , Ghrelin*/pharmacology , Arcuate Nucleus of Hypothalamus*/metabolism , Food Deprivation*/physiology , Glutamate Decarboxylase*/metabolism , Glutamate Decarboxylase*/genetics, Animals ; Male ; Mice ; Mice, Transgenic ; Agouti-Related Protein/metabolism ; Agouti-Related Protein/genetics ; Mice, Inbred C57BL |
| مستخلص: | The growth hormone secretagogue receptor (GHSR), primarily known as the receptor for the hunger hormone ghrelin, potently controls food intake, yet the specific Ghsr-expressing cells mediating the orexigenic effects of this receptor remain incompletely characterized. Since Ghsr is expressed in gamma-aminobutyric acid (GABA)-producing neurons, we sought to investigate whether the selective expression of Ghsr in a subset of GABA neurons is sufficient to mediate GHSR's effects on feeding. First, we crossed mice that express a tamoxifen-dependent Cre recombinase in the subset of GABA neurons that express glutamic acid decarboxylase 2 (Gad2) enzyme (Gad2-CreER mice) with reporter mice, and found that ghrelin mainly targets a subset of Gad2-expressing neurons located in the hypothalamic arcuate nucleus (ARH) and that is predominantly segregated from Agouti-related protein (AgRP)-expressing neurons. Analysis of various single-cell RNA-sequencing datasets further corroborated that the primary subset of cells coexpressing Gad2 and Ghsr in the mouse brain are non-AgRP ARH neurons. Next, we crossed Gad2-CreER mice with reactivable GHSR-deficient mice to generate mice expressing Ghsr only in Gad2-expressing neurons (Gad2-GHSR mice). We found that ghrelin treatment induced the expression of the marker of transcriptional activation c-Fos in the ARH of Gad2-GHSR mice, yet failed to induce food intake. In contrast, food deprivation-induced refeeding was higher in Gad2-GHSR mice than in GHSR-deficient mice and similar to wild-type mice, suggesting that ghrelin-independent roles of GHSR in a subset of GABA neurons is sufficient for eliciting full compensatory hyperphagia in mice. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.) |
| معلومات مُعتمدة: | PICT2017-3196 Fondo para la Investigación Científica y Tecnológica; 21903/PI/22 Fundación Seneca; PIBAA 28720210101241CO CONICET; NPRP13S-0209-200315 The National Qatar Research Foundation |
| فهرسة مساهمة: | Keywords: GABA; GHSR; Gad2; arcuate; ghrelin |
| المشرفين على المادة: | 0 (Receptors, Ghrelin) 0 (Ghrelin) EC 4.1.1.15 (Glutamate Decarboxylase) EC 4.1.1.15 (glutamate decarboxylase 2) 0 (Agouti-Related Protein) |
| تواريخ الأحداث: | Date Created: 20240530 Date Completed: 20240614 Latest Revision: 20240628 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1210/endocr/bqae061 |
| PMID: | 38815068 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7170 |
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| DOI: | 10.1210/endocr/bqae061 |