To efficiently deal with changes in nutrient availability across the 24-hr day, animals have evolved daily rhythms in energy metabolism and, consequently, a daily rhythm in ventilation to mediate metabolic gas exchange. Daily ventilatory rhythms have been implicated in a variety of respiratory diseases such as sleep apnea, due to time-specific occurrence of symptoms. However, it is unknown how obese physiology and intermittent hypoxia (IH), two hallmarks of sleep apnea, influence the daily rhythm in ventilation. Here, we use a dietary mouse model of obesity to determine the extent to which ventilation rhythms are influenced by obese physiology and IH. Using whole-body plethysmography, we found that obese mice chronically-fed a high-fat diet exhibit a dampened minute ventilation rhythm and decreased mean ventilation during the night-time. The obesity-associated reduction in minute ventilation was sex-specific and resulted in part from a failure of female mice to increase minute ventilation in proportion to weight gain. Moreover, we found that 5 days of daytime IH exposure minimally affected the daily rhythm in minute ventilation. We conclude that the daily rhythm in minute ventilation is attenuated by obesity in a sex-specific manner but largely unaffected by intermittent hypoxia. Taken together, these results have clinical implications for obesity-associated respiratory diseases such as obstructive sleep apnea.
This work was supported by the American Heart Association (PI Arble, 20IPA35320195) and a Marquette University Research Fellowship (Jones).
