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

BACKGROUND: Circadian rhythms in physiology optimize organismal behavior to anticipate predictable environmental changes. Modern lifestyles can cause misalignment between ≈24-hour rhythms in feeding behavior from daily environmental cycles. Feeding behavior is a potent behavioral zeitgeber (timekeeping cue). We determined how shifting the timing of feeding behavior impacts the alignment of ≈24-hour rhythms in HR and cardiac electrophysiology in wild-type (WT) and Scn5a +/ΔKPQ mice.

METHODS: Mice eat most of their daily calories during the dark cycle. We shifted limited their food access to the light cycle (light-cycle restricted feeding or L-RF). Telemetry was used to continuously record changes in electrocardiogram (ECG), core body temperature (Tb), and activity. Cosinor and cross correlation analyses were used to analyze rhythmicity and 24-hour alignment between variables.

RESULTS: L-RF for one day caused the 24-hour rhythms of the RR, QT, and PR intervals to shift 7-9 hours. The changes in the 24-hour ECG rhythms before and after the start of L-RF mirrored changes in daily body temperature (Tb) rhythm and correlated with changes in the high frequency (pHF) component of heart rate variability. Injecting mice undergoing L-RF with propranolol and atropine reduced the pHF component and caused a loss in the 24-hour rhythm in the RR interval and Tb. We identified a strong linear relation between the the QT interval and Tb. Normalizing the QT interval for Tb eliminated the 24-hour rhythm in the QT interval and identified abnormal changes in the QT interval in WT and Scn5a +/ΔKPQ mice during L-RF.

CONCLUSION: Altering the timing of daily feeding behavior reshapes 24-hour rhythms in cardiac electrophysiology in mice by modifying daily rhythms in autonomic signaling and Tb. There is a strong linear relation between the QT interval and Tb. Normalizing the QT for Tb is important for identifying QT interval prolongation independent of Tb.