Irreversible metabolic abnormalities following chronic upper airway loading.

Area of Science:

• Physiology
• Endocrinology
• Metabolism

Background:

• Obstructive sleep apnea (OSA) is linked to increased obesity risk.
• The precise mechanisms underlying this association remain unclear.
• Understanding the impact on energy expenditure and feeding hormones is crucial.

Purpose of the Study:

• To investigate the effects of upper airway obstruction and its surgical removal on respiratory homeostasis, energy expenditure, and feeding hormones.
• To analyze these effects across the sleep/wake cycle from weaning to adulthood in a rat model.

Main Methods:

• Rats underwent tracheal narrowing (obstruction) at 22 days old, with obstruction removal 14 days later.
• Energy expenditure, ventilation, and feeding hormones were monitored for 49 days before and after obstruction removal.
• Measurements included body temperature, brown adipose tissue (BAT) uncoupling protein 1 (UCP1), and feeding-related hormones (leptin, orexin, neuropeptide Y, ghrelin).

Main Results:

• Upper airway obstruction increased energy expenditure and decreased body temperature, associated with increased ventilation and reduced BAT UCP1 levels.
• Despite increased food intake, obstructed rats gained less weight due to elevated orexin, neuropeptide Y, and ghrelin.
• Obstruction removal partially normalized energy expenditure and body temperature but feeding hormone levels remained elevated, leading to increased food intake.

Conclusions:

• Maintaining respiratory homeostasis during upper airway obstruction leads to persistent metabolic and hormonal dysregulation.
• Surgical intervention alone may not fully correct energy homeostasis imbalances.
• Endocrine regulation of feeding plays a significant role in weight changes associated with OSA and its treatment.