0255 Female Mice Are Less Susceptible to the Effects of Diet-Induced Obesity on Sleep and Sleep-Disordered Breathing

Abstract

Abstract Introduction Diet-induced obesity (DIO) in male mice is a well-established model of sleep-disordered breathing (SDB). Male DIO mice manifest hypoventilation, increased apnea severity, and sleep fragmentation. The effects of DIO on breathing during sleep and sleep architecture in females have been insufficiently investigated. We hypothesized that female mice are less susceptible to the detrimental effects of DIO on sleep and SDB compared to males. Methods Full-polysomnographies were performed in 15 lean female C57BL/6J and 14 female DIO-C57BL/6J mice using a whole-body plethysmography chamber. Ventilatory response to an arousal was calculated as ratio of the average minute ventilation (VE) during each arousal (2.5s) relative to the baseline VE. Breathing stability was measured using Poincaré plots of VE. Mice were exposed to 8% CO2 to measure the hypercapnic ventilatory response (HCVR). Mice underwent 24-h metabolic studies. Results Obesity was associated with hypometabolism, indicated by reduced oxygen consumption (VO2) and CO2 production in DIO mice. VE in 8% CO2 and HCVR were significantly suppressed suggesting a decreased CO2 sensitivity in obese animals. NREM sleep duration was reduced, but REM sleep was preserved. Arousal frequency and VE during NREM and REM sleep were similar between groups. However, apnea severity was 4-fold augmented in lean females compared to DIO mice (14.7±3.9 vs 74.2±11.9 events/h; P< 0.001). In lean mice, the increased frequency of apneas was mainly attributed to sleep fragmentation since the events were predominantly post-arousals. Breathing stability during sleep was significantly increased in lean mice. Ventilatory response to an arousal was 30% increased in lean females compared to DIO group. Conclusion Our results suggest potential sex differences in the effects of DIO on breathing during sleep and sleep architecture. DIO in females appears to be less detrimental regarding SDB severity. The mechanisms underlying the augmented SDB severity in lean females are unknown, but an exacerbated CO2 responsiveness during sleep related to sleep fragmentation could play an important role. Support (if any) American Heart Association Postdoctoral Fellowship Award 828142, NHLBI grant NIH R01s HL128970, HL133100, and HL13892, American Academy of Sleep Medicine Foundation 238-BS-20, and American Thoracic Society Unrestricted Award.