Feeding Behavior Modifies Daily Rhythms in Autonomic Signaling and Core Body Temperature to Shape 24-hour Rhythms in Cardiac Electrophysiology

Abstract

AbstractCircadian rhythms in physiology and behavior are intrinsic ≈24-hour cycles regulated by biological clocks (i.e., circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. Studies suggest that circadian clock signaling in the suprachiasmatic nucleus of the hypothalamus and cardiomyocytes shape day/night rhythms in cardiac electrophysiology (i.e., RR and QT intervals). However, studies also show that the day/night rhythm of the RR and QT intervals depends on the timing of feeding in mice. This study determined the mechanisms for how feeding impacts day/night rhythms in the RR and QT intervals in mice. Telemetry was used to record electrocardiograms, core body temperature, and activity in mice during ad libitum-fed conditions and after inverting normal feeding behavior by restricting the timing of feeding to the light cycle. Light-cycle restricted feeding caused a simultaneous realignment of RR, QT, and PR intervals and body temperature to the new feeding time. Correcting the QT interval for body temperature eliminated the 24-hour rhythm in the QT interval. Estimating the impact of temperature on RR intervals did not account for the daily change in the RR interval during light-cycle restricted feeding. Cross-correlation analysis suggested daily rhythm in RR intervals correlated with heart rate variability measures but not activity. Injecting mice undergoing light cycle-restricted feeding with propranolol and atropine caused a complete loss in the 24-hour rhythm in the RR interval. We conclude that feeding behavior impacts body temperature and autonomic regulation of the heart to generate 24-hour rhythms in RR and QT intervals.New and NoteworthyOur findings demonstrate that feeding behavior is a critical timekeeper for aligning daily rhythms in cardiac electrophysiology (i.e., RR and QT intervals) in mice. The data suggest that feeding behavior shapes 24-hour rhythms in the RR interval by altering day/night rhythms in core body temperature and autonomic input to the heart. In contrast to the RR interval, the 24-hour rhythms in the QT interval are largely shaped by day/night rhythms in core body temperature.