The role of leptin signaling in the dorsomedial hypothalamus in the upper airway patency during sleep

Abstract

Obstructive sleep apnea (OSA) is a severe breathing disorder, characterized by periodic obstruction of the upper airways during sleep with eventual impact in the cardiovascular and respiratory systems as well as in the inflammatory status. OSA and its critical respiratory complications may be associated with obesity hypoventilation syndrome. Previous studies have documented the role of leptin, an adipose tissue produced hormone, as a potent respiratory stimulant. Experimental evidence has indicated that leptin may be a promising therapeutic candidate for the management of OSA. A long functional isoform of leptin receptor, LepRb, was detected in the dorsomedial hypothalamus (DMH), a critical nucleus that receives input from systems that monitor food availability. A large proportion DMH neurons express melanocortin receptor 4 (MCR4) and for this reason MCR4(+) in DMH is a highly relevant therapeutic target for OSA. In the present research project, we hypothesize that leptin regulates upper airway patency acting in the hypothalamus in an experimental model of OSA.