Leptin signaling in the dorsomedial hypothalamus couples breathing and metabolism in obesity.

ABSTRACT: 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 LEPR^b+ neurons of the dorsomedial hypothalamus (DMH) regulate metabolism and breathing in obesity. In diet-induced obese Lepr^bCre mice, chemogenetic activation of LEPR^b+ 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 t

SUBMITTER: Amorim MR 

PROVIDER: S-EPMC10804286 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature