Abstract

Objective: The circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus drives circadian rhythms in feeding and activity. Several studies suggest the SCN regulates autonomic input to the heart to generate day-night rhythms in heart rate. Hypothesis: The circadian rhythm in feeding generates day-night rhythms in autonomic input to the heart and heart rate. Methodology: Mice (n=6/sex) were implanted with telemetry probes to continuously record heart rate, core body temperature, and activity in thermoneutral housing conditions. Mice were housed in a 12 h light: 12 h dark cycle (LD) with ad libitum access to food (ALF). In these conditions, mice primarily eat during the dark cycle. Mice were subjected to light phase time-restricted feeding (TRF) for 5 days. This forces the mice to eat during the light cycle. We quantified changes in autonomic input to the heart by injecting mice with the autonomic receptor inhibitors propranolol and methylatropine. To determine if circadian rhythms generate day-night rhythms in autonomic input to the heart, TRF mice were switched from LD to constant darkness (DD) and then returned to ALF in DD. Results: ALF mice housed in LD had 24-hour rhythms in autonomic input to the heart, heart rate, and activity that all peaked in alignment during the dark cycle. One day after starting TRF, the phase of the 24-hour rhythms in heart rate but not activity shifted by 8-10 hours to align with feeding during the light phase. Switching TRF mice in LD to DD did not alter the phase or amplitude of the day-night rhythms in autonomic input to the heart, heart rate, or activity. Returning the TRF mice in DD to ALF showed the autonomic input to the heart and heart rate re-aligned with the free running rhythm in activity. Conclusions: Day-night rhythms in heart rate and autonomic input to the heart align with activity in LD and DD in ad libitum fed but not time-restricted fed conditions. These data demonstrate that feeding behavior, not SCN-signaling or activity rhythms, drives day-night rhythms in autonomic input to the heart and heart rate.

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