0268 Abnormal Growth and Energy Metabolism Induced by Chronic Upper Airway Obstruction is Associated with Impairment of Somatotropic Axis in rats Academic Article uri icon

abstract

  • Introduction Children with sleep-disordered breathing (SDB) often exhibit growth retardation, and the upper airway obstruction (AO) rat model mimics many of the features of human SDB including the abnormal sleep and growth retardation. The mechanisms linking AO-induced sleep, growth impediment, and energy metabolism abnormalities are poorly understood. Here, we investigated the role of somatotropic hormonal profile and energy metabolism during sleep/wake cycle in unrestrained juvenile rats. Methods The tracheae of 22-day-old rats were narrowed; on day 14 the AO group was randomized; obstruction removal OR) of the silicon band was performed on half of AO animals. All animals were monitored for 7 weeks, metabolic profiles, food intake were measured using a high-definition metabolic system, and ventilation was measured by plethysmography. Following euthanasia at 7 weeks, bone-related mediators were analyzed. Results The AO group gained 40% less body weight compared to the controls, despite 20% elevation of food intake, the OR group gained 6% less body weight but still ate more; The increased energy in AO/OR led to up regulation of ventilation. Up regulation of bone orexin receptor 1 (OX1R) was associated with decreased bone SOX9, increased peroxisome proliferator-activated receptor gamma (PPARγ), and marrow adipogenesis, while at the same time systemic adipose volume was reduced in AO animals. Interestingly, OR only partly improved bone volume, bone mass, and growth plate width, and didn’t prevent marrow adipogenesis. Phosphorylated activated protein kinase (pAMPK) ratio was reduced in AO and was partially improved in OR. Conclusion Abnormal growth and energy metabolism in AO are associated with alteration in circulating anabolic hormones. Obstruction removal was associated with significant elevation in marrow adipogenesis although trachea diameter was statistically similar to that of the control group. These results provide evidence of altered hormonal regulation at the level of the bone and implicate suppression of anabolic hormones leading to abnormal energy metabolism and growth retardation during chronic upper airway obstruction. Support (If Any) The Israel Science Foundation Grant No. 31/14.

publication date

  • January 1, 2018

published in