Effects of leptin and obesity on the upper airway function

Mikhael Polotsky, Ahmed S. Elsayed-Ahmed, Luis Pichard, Christopher C. Harris, Philip L. Smith, Hartmut Schneider, Jason P. Kirkness, Vsevolod Polotsky, Alan R. Schwartz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1637-1643
Number of pages7
JournalJournal of applied physiology
Volume112
Issue number10
DOIs
StatePublished - May 15 2012

Keywords

  • Leptin
  • Neuromuscular control
  • Ob-/ob-
  • Obstructive sleep apnea
  • Pharynx

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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