TY - JOUR
T1 - Leptin and the control of pharyngeal patency during sleep in severe obesity
AU - Shapiro, Steven D.
AU - Chin, Chien Hung
AU - Kirkness, Jason P.
AU - McGinley, Brian M.
AU - Patil, Susheel P.
AU - Polotsky, Vsevolod Y.
AU - Biselli, Paolo Jose Cesare
AU - Smith, Philip L.
AU - Schneider, Hartmut
AU - Schwartz, Alan R.
PY - 2014/5/15
Y1 - 2014/5/15
N2 - 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/m2, age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m2, 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 (AVImax), inspired minute ventilation (AVI), and pharyngeal critical pressure (APCRIT) 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 AVImax (r2 = 0.44, P < 0.001), AVI (r2 = 0.40, P < 0.001), and APCRIT (r2 = 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.
AB - 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/m2, age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m2, 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 (AVImax), inspired minute ventilation (AVI), and pharyngeal critical pressure (APCRIT) 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 AVImax (r2 = 0.44, P < 0.001), AVI (r2 = 0.40, P < 0.001), and APCRIT (r2 = 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.
KW - Leptin
KW - Obesity
KW - Obstructive sleep apnea
KW - Upper airway control
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U2 - 10.1152/japplphysiol.00958.2013
DO - 10.1152/japplphysiol.00958.2013
M3 - Article
C2 - 24557793
AN - SCOPUS:84901192929
SN - 8750-7587
VL - 116
SP - 1334
EP - 1341
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 10
ER -