Abstract
Pediatric obstructive sleep-disordered breathing is associated with growth retardation, but also with obesity that has a tendency to persist following treatment. We investigated the effect of upper airways obstruction (AO) and of obstruction removal (OR) in juvenile rats on gut-derived ghrelin and related hypothalamic factors, feeding, and growth hormone (GH) homeostasis. Here, we show that after seven weeks of AO, animals gained less weight compared to controls, despite an increase in food intake due to elevated ghrelin and hypothalamic feeding factors. OR rats who had complete restoration of tracheal diameter, consumed more food due to increased ghrelin and exhibited growth retardation due to deregulation of GH homeostasis. This study is the first to show dysregulation of the hormonal axes controlling feeding behavior and growth that are not fully restored following OR. Thus, surgical treatment by itself may not be sufficient to prevent post-surgical increased food intake and growth retardation.
Highlights
We have previously shown that the juvenile upper airway obstruction (AO) rat model mimics many of the features of pediatric SDB including sleep fragmentation and growth retardation[8,9,10]
Trachea cross-sectional area according to histology analysis was reduced by 70% (p < 0.001) in airways obstruction (AO); after obstruction removal (OR) trachea cross-sectional area was 20% (p < 0.05) smaller than in controls (Supplementary Fig. S1)
Elevation of gut-derived ghrelin and its hypothalamic mediators was associated with hyperphagia and altered hypothalamus-pituitary growth hormone (GH) axis due to down-regulation of growth hormone releasing hormone (GHRH) and up-regulation of somatostatin
Summary
We have previously shown that the juvenile upper airway obstruction (AO) rat model mimics many of the features of pediatric SDB including sleep fragmentation and growth retardation[8,9,10]. To the best of our knowledge, the role of the appetite-related neuroendocrine factors on eating behavior in AO and after obstruction removal (OR) have not been well-characterized. Feeding is regulated by the gut-derived hormone ghrelin, and by the hypothalamic release of orexin and ghrelin[18,19,20,21]. We hypothesized that AO leads to sustained elevation of gut-derived ghrelin, which, on one hand, causes desensitization of the hypothalamic-pituitary-GH axis while, on the other hand, increases feeding behavior. Increased feeding after AO, whether treated or untreated, is related to elevated gut-derived ghrelin hormone and its hypothalamic factors and to up regulation of hypothalamic orexin. Indicates that upper airway obstruction elicits persistent neurohumoral derangements that are “stamped” on the hypothalamic pituitary axis of feeding and growth. Our data suggest that the surgical treatment per se may not be sufficient to prevent the post-surgical trend for increase in body weight and growth retardation
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