Leptin and the control of pharyngeal patency during sleep in severe obesity

J Appl Physiol (1985). 2014 May 15;116(10):1334-41. doi: 10.1152/japplphysiol.00958.2013. Epub 2014 Feb 20.


Rationale: Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep.

Methods: An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions.

Results: Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth.

Conclusion: Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.

Keywords: leptin; obesity; obstructive sleep apnea; upper airway control.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Female
  • Humans
  • Leptin / blood*
  • Obesity, Morbid / complications
  • Obesity, Morbid / physiopathology*
  • Pharynx / physiopathology*
  • Pulmonary Ventilation*
  • Sleep Apnea, Obstructive / etiology
  • Sleep Apnea, Obstructive / physiopathology*
  • Sleep*


  • Leptin