| Texto completo | |
| Autor(es): Mostrar menos - |
Amorim, Mateus R.
;
Wang, Xin
;
Aung, O.
;
Bevans-Fonti, Shannon
;
Anokye-Danso, Frederick
;
Ribeiro, Caitlin
;
Escobar, Joan
;
Freire, Carla
;
Pho, Huy
;
Dergacheva, Olga
;
Branco, Luiz G. S.
;
Ahima, Rexford S.
;
Mendelowitz, David
;
Polotsky, Vsevolod Y.
Número total de Autores: 14
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CELL REPORTS; v. 42, n. 12, p. 20-pg., 2023-11-30. |
| Resumo | |
Mismatch between CO2 production (VCO2) and respiration underlies the pathogenesis of obesity hypoventila-tion. 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) regu-late 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 chemo-genetic 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). Admin-istration 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. (AU) | |
| Processo FAPESP: | 19/13249-3 - O papel da sinalização da leptina no hipotálamo dorsomedial na permeabilidade das vias aéreas superiores durante o sono |
| Beneficiário: | Mateus Ramos Amorim |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado |