Female gender exacerbates respiratory depression in leptin-deficient obesity

Vsevolod Y. Polotsky, Jessica A. Wilson, Marc C. Smaldone, Abby S. Haines, Patricia D. Hurn, Clarke G. Tankersley, Philip L. Smith, Alan R. Schwartz, Christopher P. O'Donnell

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Obese females are less predisposed to sleep-disordered breathing and have higher serum leptin levels than males of comparable body weight. Because leptin is a powerful respiratory stimulant, especially during sleep, we hypothesized that the elevated leptin level is necessary to maintain normal ventilatory control in obese females. We examined ventilatory control during sleep and wakefulness in male and female leptin-deficient obese C57BL/6J-Lepob mice, wild-type C57BL/6J mice with dietary-induced obesity and high serum leptin levels, and normal weight wild-type C57BL/6J mice. Both male and female C57BL/6J-Lepob mice had depressed hypercapnic ventilatory response (HCVR) in comparison with wildtype animals. In comparison with male C57BL/6J-Lepob mice, female C57BL/6J-Lepob mice had reduced HCVR and respiratory drive (a ratio of tidal volume to inspiratory time) both during non-rapid eye movement (NREM) sleep and wakefulness. In contrast, the HCVR did not differ between sexes in wild-type mice during NREM sleep and wakefulness, but was lower in females during REM sleep. Thus, leptin deficiency in female obesity is even more detrimental to hypercapnic ventilatory control during wakefulness and NREM sleep than in obese, leptin-deficient males.

Original languageEnglish (US)
Pages (from-to)1470-1475
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Issue number8 I
StatePublished - Oct 15 2001
Externally publishedYes


  • Estradiol
  • Leptin
  • Obesity
  • Sleep
  • Ventilation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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