TY - JOUR
T1 - Effects of leptin and obesity on the upper airway function
AU - Polotsky, Mikhael
AU - Elsayed-Ahmed, Ahmed S.
AU - Pichard, Luis
AU - Harris, Christopher C.
AU - Smith, Philip L.
AU - Schneider, Hartmut
AU - Kirkness, Jason P.
AU - Polotsky, Vsevolod
AU - Schwartz, Alan R.
PY - 2012/5/15
Y1 - 2012/5/15
N2 - Obesity is associated with alterations in upper airway collapsibility during sleep. Obese, leptin-deficient mice demonstrate blunted ventilatory control, leading us to hypothesize that (1) obesity and leptin deficiency would predispose to worsening neuromechanical upper airway function and that (2) leptin replacement would acutely reverse neuromuscular defects in the absence of weight loss. In age-matched, anesthetized, spontaneously breathing C57BL/6J (BL6) and ob-/ob- mice, we characterized upper airway pressure-flow dynamics during ramp decreases in nasal pressure (P N) to determine the passive expiratory critical pressure (PCRIT) and active responses to reductions in PN, including the percentage of ramps showing inspiratory flow limitation (IFL; frequency), the PN threshold at which IFL developed, maximum inspiratory airflow (VI max), and genioglossus electromyographic (EMG GG) activity. Elevations in body weight were associated with progressive elevations in P CRIT (0.1 ± 0.02 cmH 2O/g), independent of mouse strain. P CRIT was also elevated in ob-/ob- compared with BL6 mice (1.6 ± 0.1 cmH 2O), independent of weight. Both obesity and leptin deficiency were associated with significantly higher IFL frequency and P N threshold and lower VI max. Very obese ob-ob- mice treated with leptin compared with nontreated mice showed a decrease in IFL frequency (from 63.5 ± 2.9 to 30.0 ± 8.6%) and PN threshold (from ±0.8 ± 1.1 to ±5.6 ± 0.8 cmH 2O) and increase in VImax (from 354.1 ± 25.3 to 659.0 ± 71.8 μl/s). Nevertheless, passive P CRIT in leptin-treated mice did not differ significantly from that seen in nontreated ob-/ob- mice. The findings suggest that weight and leptin deficiency produced defects in upper airway neuromechanical control and that leptin reversed defects in active neuromuscular responses acutely without reducing mechanical loads.
AB - Obesity is associated with alterations in upper airway collapsibility during sleep. Obese, leptin-deficient mice demonstrate blunted ventilatory control, leading us to hypothesize that (1) obesity and leptin deficiency would predispose to worsening neuromechanical upper airway function and that (2) leptin replacement would acutely reverse neuromuscular defects in the absence of weight loss. In age-matched, anesthetized, spontaneously breathing C57BL/6J (BL6) and ob-/ob- mice, we characterized upper airway pressure-flow dynamics during ramp decreases in nasal pressure (P N) to determine the passive expiratory critical pressure (PCRIT) and active responses to reductions in PN, including the percentage of ramps showing inspiratory flow limitation (IFL; frequency), the PN threshold at which IFL developed, maximum inspiratory airflow (VI max), and genioglossus electromyographic (EMG GG) activity. Elevations in body weight were associated with progressive elevations in P CRIT (0.1 ± 0.02 cmH 2O/g), independent of mouse strain. P CRIT was also elevated in ob-/ob- compared with BL6 mice (1.6 ± 0.1 cmH 2O), independent of weight. Both obesity and leptin deficiency were associated with significantly higher IFL frequency and P N threshold and lower VI max. Very obese ob-ob- mice treated with leptin compared with nontreated mice showed a decrease in IFL frequency (from 63.5 ± 2.9 to 30.0 ± 8.6%) and PN threshold (from ±0.8 ± 1.1 to ±5.6 ± 0.8 cmH 2O) and increase in VImax (from 354.1 ± 25.3 to 659.0 ± 71.8 μl/s). Nevertheless, passive P CRIT in leptin-treated mice did not differ significantly from that seen in nontreated ob-/ob- mice. The findings suggest that weight and leptin deficiency produced defects in upper airway neuromechanical control and that leptin reversed defects in active neuromuscular responses acutely without reducing mechanical loads.
KW - Leptin
KW - Neuromuscular control
KW - Ob-/ob-
KW - Obstructive sleep apnea
KW - Pharynx
UR - http://www.scopus.com/inward/record.url?scp=84862080026&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862080026&partnerID=8YFLogxK
U2 - 10.1152/japplphysiol.01222.2011
DO - 10.1152/japplphysiol.01222.2011
M3 - Article
C2 - 22345430
AN - SCOPUS:84862080026
SN - 8750-7587
VL - 112
SP - 1637
EP - 1643
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 10
ER -