Abstract

Behavioral and physiological circadian rhythms are controlled by endogenous oscillators in animals. Voluntary wheel-running in rodents is thought to be an appropriate model of aerobic exercise in humans. We evaluated the effects of chronic voluntary exercise on the circadian system by analyzing temporal profiles of feeding, core body temperature, plasma hormone concentrations and peripheral expression of clock and clock-controlled genes in mice housed under sedentary (SED) conditions or given free access to a running-wheel (RW) for four weeks. Voluntary wheel-running activity advanced the circadian phases of increases in body temperature, food intake and corticosterone secretion in the mice. The circadian expression of clock and clock-controlled genes was tissue- and gene-specifically affected in the RW mice. The temporal expression of E-box-dependent circadian clock genes such as Per1, Per2, Nr1d1 and Dbp were slightly, but significantly phase-advanced in the liver and white adipose tissue, but not in brown adipose tissue and skeletal muscle. Peak levels of Per1, Per2 and Nr1d1 expression were significantly increased in the skeletal muscle of RW mice. The circadian phase and levels of hepatic mRNA expression of the clock-controlled genes that are involved in cholesterol and fatty acid metabolism significantly differed between SED and RW mice. These findings indicated that endogenous clock-governed voluntary wheel-running activity provides feedback to the central circadian clock that systemically governs behavioral and physiological rhythms.

Highlights

  • Most mammals exhibit various behavioral and physiological circadian rhythms such as sleepwake cycles, locomotor activity, feeding behaviour, core body temperature (Tb), bloodPLOS ONE | DOI:10.1371/journal.pone.0116476 January 23, 2015Wheel-Running Activity Modulates Circadian Rhythm pressure, immune functions, hormonal secretion and glucose and lipid metabolism that are controlled by endogenous oscillators

  • The relative weights of WAT and BAT to total body weight significantly decreased in running wheels (RW) mice (t = 0.03, P < 0.01 and t = 1.16, P < 0.05, respectively), whereas those of the liver, skeletal muscle, heart and lung were similar between SED and RW mice (t = 0.85, P = 0.579; t = 1.03, P = 0.959; t = 1.39, P = 0.114 and t = 2.90, P = 0.852, respectively; Table 1)

  • The present study found that chronic free access to a running-wheel affects behavioral and physiological circadian rhythms in addition to the peripheral expression of clock and clockcontrolled genes in mice

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Summary

Introduction

Most mammals exhibit various behavioral and physiological circadian rhythms such as sleepwake cycles, locomotor activity, feeding behaviour, core body temperature (Tb), bloodPLOS ONE | DOI:10.1371/journal.pone.0116476 January 23, 2015Wheel-Running Activity Modulates Circadian Rhythm pressure, immune functions, hormonal secretion and glucose and lipid metabolism that are controlled by endogenous oscillators. Most mammals exhibit various behavioral and physiological circadian rhythms such as sleepwake cycles, locomotor activity, feeding behaviour, core body temperature (Tb), blood. The mammalian circadian clock system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus and peripheral oscillators in most tissues. Many studies at the molecular level have found that circadian oscillators in both the SCN and peripheral tissues are driven by negative feedback loops comprising the periodic expression of clock genes [1,2]. The environmental light-dark (LD) cycle is the critical time cue for daily resetting of the central clock in the SCN, which entrains the phase of the pacemaker to the environment [1,2]. Peripheral clocks are entrained to the SCN by systemic time cues such as neuronal, humoral and other signals including body temperature [1,2]

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