0785 Effects of Sympathetic Activity on Energy Intake in Upper Airway Obstruction/ Obstruction Removal Mouse Model

Abstract Introduction Pediatric sleep-disordered breathing (SDB) increases the risk of accelerated body weight gain if the post-treatment weight is uncontrolled. Upper airway obstruction (AO)/ obstruction removal (OR) in rodents mimics many SDB characteristics, including increased food intake. Orexin, a peptide produced by hypothalamic neurons, emerged as one of the critical orchestrators of breathing and deregulation of feeding in AO/ OR animals. It is possible that orexin affects energy expenditure due to increased sympathetic activation of brown fat uncoupling protein-1 (UCP-1) that may contribute to weight gain following OR. We hypothesize that AO/OR induces elevation of sympathetic activity that leads to persistent increased feeding behavior. Methods We employed a mouse model to examine the impact of AO followed by OR two weeks later. The mice were observed for an additional eight to twelve weeks, roughly equivalent to two decades in human terms. We examined the impact of AO/OR on feeding hormones, respiration (assessed through plethysmography), energy expenditure and intake (monitored in metabolic cages), nutritional preferences for a high glycemic index diet, and thermography using infrared cameras. We studied the impact of specific β3-adrenergic receptor blockade (L-748,337, 5 mg/kg) on energy balance. Results The heightened energy expenditure in AO was associated with an augmented breathing workload, elevated plasma norepinephrine levels, increased UCP1 levels, and an enhanced effort in breathing to maintain acid-base homeostasis. Elevated orexin and ghrelin levels were associated with increased energy intake. The AO mice's daily dietary glycemic index intake exceeded that of the control group by more than 250% compared to a low glycemic index diet. OR maintained heightened food intake, preference for a high glycemic index diet, and elevated energy expenditure despite normalized ventilation, associated with increased interscapular temperatures and brown fat UCP1 levels. The administration of L-748,337 reduces interscapular temperatures and decreases energy intake in the OR group. Conclusion The need to maintain respiratory homeostasis in AO animals is associated with abnormal energy metabolism and thermogenic capacity that are not reversible following OR. Obstruction removal is linked to persistent heightened feeding and increased sympathetic activity, even with normalized breathing and energy needs. Support (if any) Israel Science Foundation Grant No. 164/2018.