| First Author | Amorim MR | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 12 | Pages | 113512 |
| PubMed ID | 38039129 | Mgi Jnum | J:355293 |
| Mgi Id | MGI:7574059 | Doi | 10.1016/j.celrep.2023.113512 |
| Citation | Amorim MR, et al. (2023) Leptin signaling in the dorsomedial hypothalamus couples breathing and metabolism in obesity. Cell Rep 42(12):113512 |
| abstractText | Mismatch between CO(2) production (Vco(2)) 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 LEPR(b)+ neurons of the dorsomedial hypothalamus (DMH) regulate metabolism and breathing in obesity. In diet-induced obese Lepr(b)Cre mice, chemogenetic activation of LEPR(b)+ DMH neurons increases minute ventilation (Ve) during sleep, the hypercapnic ventilatory response, Vco(2), and Ve/Vco(2), 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 LEPR(b)+ 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 LEPR(b)+ DMH neurons and abolishes metabolic and respiratory responses to leptin. These findings indicate that LEPR(b)+ DMH neurons match breathing to metabolism through serotonergic pathways to prevent obesity-induced hypoventilation. |
