Chronic circadian disruption alters cardiac function and glucose regulation in mice.

Abstract

Cardiometabolic disease is a leading cause of death worldwide. One factor that may contribute to the risk, onset, and severity of symptoms is disrupted circadian rhythms. Our study uses two strains of mice to further elucidate this relationship: healthy controls, and a mouse model of insulin resistance with short freerunning periods (~ 22.75 h) and enlarged hearts, raised in either a 24-h or 22.75-h LD cycle. Through glucose and insulin tolerance tests, routine electrocardiograms from one to four months old, and histology, we reveal worse cardiometabolic health outcomes for mice gestated and housed in a mismatched LD cycle compared to those in an LD cycle that matches their endogenous rhythm. This was characterized by heightened blood glucose levels following a glucose or insulin bolus, altered electrophysiological parameters of the cardiac waveform, and increased cardiomyocyte size. Circadian disruption due to work/social schedules or circadian-related disorders in people is often confounded with other unhealthy lifestyles. The present study demonstrates that circadian disruption on its own can lead to adverse health states.