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

Diet-induced obesity (DIO) in male mice is a well-established model of sleep-disordered breathing (SDB). Male DIO mice manifest obesity hypoventilation, increased apnea severity, and sleep fragmentation. The effects of DIO on breathing during sleep and sleep architecture in females have been insufficiently investigated. In this study, we aimed to compare the breathing and sleep patterns of lean and obese female mice of similar genetic background. We hypothesized that female mice are less susceptible to the detrimental effects of DIO on sleep and SDB compared to males. Full-polysomnographies were performed in 15 lean female C57BL/6J and 14 female DIO-C57BL/6J mice using a whole-body plethysmography chamber. Arousals from sleep and apneas were manually scored. Ventilatory response to an arousal was calculated as ratio of the peak minute ventilation (V E ) during each arousal relative to the baseline V E (from 2.5s to 5s preceding the arousal). Breathing stability was measured using Poincaré plots of V E . Mice were acutely exposed to 8% CO 2 to measure the hypercapnic ventilatory response (HCVR). An additional 10 mice (5 each/group) underwent 24-h metabolic studies. We found that obesity was associated with hypometabolism, indicated by reduced oxygen consumption (VO 2 ) and CO 2 production in DIO mice. VE in 8% CO 2 and HCVR were significantly suppressed suggesting a decreased CO 2 sensitivity in obese animals. NREM sleep duration was reduced, but REM sleep was preserved. Arousal frequency was similar between groups (~78 events/h). DIO mice hypoventilated during NREM sleep. 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). Breathing stability during sleep was significantly increased in lean mice. Ventilatory response to an arousal was higher in lean females, but it was attributed to an overall increased V E during arousal and at baseline. 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 could play an important role. American Heart Association Postdoctoral Fellowship Award 828142 (to L.J.K.), NHLBI grant NIH R01 HL128970, R01 HL133100, and R01 HL13892 (to V.Y.P.), American Academy of Sleep Medicine Foundation 238-BS-20, and American Thoracic Society Unrestricted Award (to L.V.P.) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.