Effects of leptin and obesity on the upper airway function

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 (PN) 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 (Vimax), and genioglossus electromyographic (EMGGG) activity. Elevations in body weight were associated with progressive elevations in PCRIT (0.1 ± 0.02 cmH2O/g), independent of mo...