| Autor: |
Mateus R. Amorim, Xin Wang, O. Aung, Shannon Bevans-Fonti, Frederick Anokye-Danso, Caitlin Ribeiro, Joan Escobar, Carla Freire, Huy Pho, Olga Dergacheva, Luiz G.S. Branco, Rexford S. Ahima, David Mendelowitz, Vsevolod Y. Polotsky |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 42, Iss 12, Pp 113512- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.113512 |
| Popis: |
Summary: Mismatch between CO2 production (Vco2) and respiration underlies the pathogenesis of obesity hypoventilation. Leptin-mediated CNS pathways stimulate both metabolism and breathing, but interactions between these functions remain elusive. We hypothesized that LEPRb+ neurons of the dorsomedial hypothalamus (DMH) regulate metabolism and breathing in obesity. In diet-induced obese LeprbCre mice, chemogenetic activation of LEPRb+ DMH neurons increases minute ventilation (Ve) during sleep, the hypercapnic ventilatory response, Vco2, and Ve/Vco2, indicating that breathing is stimulated out of proportion to metabolism. The effects of chemogenetic activation are abolished by a serotonin blocker. Optogenetic stimulation of the LEPRb+ DMH neurons evokes excitatory postsynaptic currents in downstream serotonergic neurons of the dorsal raphe (DR). Administration of retrograde AAV harboring Cre-dependent caspase to the DR deletes LEPRb+ DMH neurons and abolishes metabolic and respiratory responses to leptin. These findings indicate that LEPRb+ DMH neurons match breathing to metabolism through serotonergic pathways to prevent obesity-induced hypoventilation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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