Female gender exacerbates respiratory depression in leptin-deficient obesity

Obese females are less predisposed to steep-disordered breathing and have h igher serum leptin levels than males of comparable body weight. Because lep tin is, a powerful respiratory stimulant, especially during steep, we hypot hesized that the elevated leptin level is necessary to maintain normal vent ilatory control in obese females. We examined ventilatory control during sl eep and wakefulness in male and female leptin-deficient obese C57BL/6J-Lep( ob) mice, wild-type C57BL/6J mice with dietary-induced obesity and high ser um leptin levels, and normal weight wild-type C57BL/6J mice. Both male and female C57BL/6J-Lep(ob) mice had depressed hypercapnic ventilatory response (HCVR) in comparison with wildtype animals. In comparison with male C57BL/ 61-Lep(ob) mice, female C57BL/6J-Lep(ob) mice had reduced HCVR and respirat ory drive (a ratio of tidal volume to inspiratory time) both during non-rap id eye movement (NREM) sleep and wakefulness. In contrast, the HCVR did not differ between sexes in wild-type mice during NREM steep and wakefulness, but was lower in females during REM sleep. Thus, leptin deficiency in femal e obesity is even more detrimental to hypercapnic ventilatory control durin g wakefulness and NREM sleep than in obese, leptin-deficient males.