Beneficial effects of voluntary wheel running on activity rhythms, metabolic state, and affect in a diurnal model of circadian disruption

Carmel Bilu,Vicktoria Vishnevskia-Dai,William J Schwartz,Noga Kronfeld-Schor,Haim Einat,Paul Zimmet

doi:10.1038/s41598-022-06408-z

Abstract

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). Voluntary exercise strengthened general activity rhythms, improved memory and lowered anxiety- and depressive-like behaviors, enhanced oral glucose tolerance, and decreased plasma insulin levels and liver weight. Animals with access to a running wheel had larger heart weight and heart/body weight ratio, and thicker left ventricular wall. Our results demonstrate that exercising ameliorates pathological-like daily rhythms in activity and blood glucose levels, glucose tolerance and depressive- and anxiety-like behaviors in the sand rat model, supporting the important role of physical activity in modulating the “circadian syndrome” and circadian rhythm-related diseases. We suggest that the utilization of a diurnal rodent animal model may offer an effective way to further explore metabolic, cardiovascular, and affective-like behavioral changes related to chronodisruption and their underlying mechanisms.

Highlights

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM)
The presence of a running wheel in the cage had a significant effect on baseline blood glucose levels and on glucose tolerance, with the No wheels group showing significantly higher blood glucose levels than the Wheels group both at baseline (T-test, t = − 4.2, p = 0.0004) and 120 min after oral glucose administration in the oral glucose tolerance test (T-test, t = − 3.31, p = 0.004) (Fig. 2)
Our results show that voluntary wheel running for 11 weeks inhibits the development of the “circadian syndrome” in fat sand rats housed indoors in standard laboratory conditions

Summary

Introduction

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). A “central” or “master” clock in the hypothalamus of the brain (suprachiasmatic nucleus [SCN]) synchronizes “peripheral” clocks found in cells, tissues, and organs throughout the brain and body to regulate metabolism and temporal physiology[7,8] This network of clocks is capable of adaptively re-aligning its oscillatory components under changing conditions, including to signals such as, e.g., temperature, blood glucose and oxygen levels, and glucocorticoids. Deregulated circadian rhythms in skeletal muscles are associated with reduced glucose tolerance, as well as increased rates of diabetes and C VD31,32

Methods

Results

Conclusion