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Obesity elicits a sex‐specific attenuation of the daily rhythm in ventilation in mice chronically fed a high‐fat diet

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.