Involvement of the Endocrine System in Regulation of Respiration and Energy metabolism in Mice Following Trachea Narrowing
2Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Israel
3Sleep-Wake Disorders Unit, Soroka University Medical Center, Israel
Obstructive sleep-disordered breathing (SDB) is a prevalent pediatric syndrome characterized by intermittent hypoxia, hypercapnia, and abnormal sleep. In absence of treatment, SDB may have serious consequences on longitudinal growth, body weight, energy metabolism, cardiovascular and neurobehavioral abnormalities and disturbance in the homeostasis of the growth hormone, ghrelin and leptin. The involvement of the endocrine system and the mechanism that causes growth retardation following SDB are not clear.
Our main hypothesis is that upper airway obstruction causes an increase in hypothalamic orexin release, which plays an essential role in maintaining respiration but also elicits persistent somatotropic axis, sleep, and homeostatic feeding abnormalities.
Using a unique, novel, AO-obstruction removal (OR) mouse model, we show here that the narrowing of the trachea causes a decrease in lung ventilation and an increase in food consumption compared to control mice. Orexin levels were increased by more than 70 percent. This was accompanied by an increase of more than 26 percent in ghrelin levels. On the other hand, leptin levels were decreased by more than 45 percent. This results can be explained by adaptive behaviors, including food intake.
This novel mechanistic study will examine important aspects related to respiratory function and disorders of energy metabolism in a mouse model that simulates some of the clinical features of SBD. Results obtained of this study will elucidate the role of orexin in the dysregulation of sleep, somatotropic axis, and homeostatic feeding.