0036 UPPER AIRWAY OBSTRUCTION AND OBSTRUCTION REMOVAL ARE ASSOCIATED WITH ABNORMAL ENERGY METABOLISM AND CHANGES IN GROWTH HORMONE AXIS IN RATS Academic Article uri icon

abstract

  • Introduction Adenotonsillectomy in children with sleep-disordered breathing (SDB) has been reported to accelerate body weight and increased risk for obesity despite normalization of sleep and respiration. The mechanisms linking upper airway obstruction (AO) and obstruction removal (OR)-induced sleep and energy metabolism abnormalities are poorly understood. Here, we investigated the effect of AO and OR on diurnal rhythms of ghrelin and its related hypothalamic mediator’s factors on sleep, feeding behavior, and hypothalamus-pituitary-growth hormone (GH) axis. Methods The tracheae of 22-day-old rats were narrowed (AO); obstruction removal (OR) was performed 2 weeks following surgery on half of the AO group randomly selected, and animals were observed for 7 weeks. Results 3D magnetic resonance imaging shows that AO trachea diameter was reduced by 44% and OR trachea diameter was similar to that of controls. Following 7-week observation period AO exhibited fragmented sleep, and reduced NREM, REM duration, and slow wave activity power. AO gained 48% less body weight despite 35% elevation of daily food intake (p<0.001). Food intake remained 12% higher (p<0.01) in OR despite the normal sleep and respiratory activity. Circulating ghrelin and hypothalamic NPY increased by >140% (p<0.01) and >60% (p<0.01) in AO and OR groups, respectively. Hypothalamic GH secretagogue receptor 1α protein increased by 40% in AO and OR (p<0.01) and cumulative food intake increased by 300% following administration of ghrelin (30 ng/kg i.p.) in all groups (p<0.001). Hypothalamic GH-releasing hormone mRNA was down regulated and somatostatin up regulated in AO and OR groups. Total and mean concentrations of GH were reduced by 60% and its pulsatility pattern was almost completely abolished. Both liver and circulating IGF-1 decreased by 50% and 15% in AO and OR, respectively. Conclusion Insufficient body weight gain, abnormal sleep, and higher energy intake in AO are related to elevation in circulating ghrelin and its hypothalamic mediator’s factors. Following OR gut ghrelin was still higher and animals continue to consume more energy andhave abnormal GH homeostasis. Here, we provide evidence that altered hypothalamus-pituitary hormonal axis lead increased risk for obesity and growth retardation. Support (If Any) Supported by the Israel Science Foundation grant No. 31/14.

publication date

  • January 1, 2017

published in