Hyperleptinemia , respiratory drive and hypercapnic response in obese patients

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnea or obesity-hypoventilation syndrome. Objective: To assess by multivariate analysis the possible association between respiratory center impairment and levels of serum leptin. Methods: Three hundred and sixty four obese subjects (BMI ≥30 kg/m) had the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (P0.1, minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction by spirometry were excluded. Results: Two hundred and forty-five subjects were included in the analysis. Lung volumes, age, log leptin levels, PetCO2, % body fat and minimal nocturnal saturation were predictors for baseline P0.1 (R = 0.222; p < 0.001). One hundred and eighty six subjects performed hypercapnic response test; log leptin levels were predictors for hypercapnic response in men (R =0.051; p=0.027 for P0.1), but not in women. Conclusions: Hyperleptinemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory center. Word count of abstract: 199