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Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle.

ABSTRACT: The existence and maintenance of biological rhythms linked to the 24-h light-dark cycle are essential to the health and functioning of an organism. Although much is known concerning central clock mechanisms, much less is known about control in peripheral tissues. In this study, circadian regulation of gene expression was examined in rat skeletal muscle. A rich time series involving 54 animals euthanized at 18 distinct time points within the 24-h cycle was performed, and mRNA expression in gastrocnemius muscles was examined using Affymetrix gene arrays. Data mining identified 109 genes that were expressed rhythmically, which could be grouped into eight distinct temporal clusters within the 24-h cycle. These genes were placed into 11 functional categories, which were examined within the context of temporal expression. Transcription factors involved in the regulation of central rhythms were examined, and eight were found to be rhythmically expressed in muscle. Because endogenous glucocorticoids are a major effector of circadian rhythms, genes identified here were compared with those identified in previous studies as glucocorticoid regulated. Of the 109 genes identified here as circadian rhythm regulated, only 55 were also glucocorticoid regulated. Examination of transcription factors involved in circadian control suggests that corticosterone may be the initiator of their rhythmic expression patterns in skeletal muscle.

SUBMITTER: Almon RR

PROVIDER: S-EPMC2576101 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle.

Almon Richard R RR Yang Eric E Lai William W Androulakis Ioannis P IP Ghimbovschi Svetlana S Hoffman Eric P EP Jusko William J WJ Dubois Debra C DC

American journal of physiology. Regulatory, integrative and comparative physiology 20080730 4

The existence and maintenance of biological rhythms linked to the 24-h light-dark cycle are essential to the health and functioning of an organism. Although much is known concerning central clock mechanisms, much less is known about control in peripheral tissues. In this study, circadian regulation of gene expression was examined in rat skeletal muscle. A rich time series involving 54 animals euthanized at 18 distinct time points within the 24-h cycle was performed, and mRNA expression in gastro ...[more]

PMID: 18667713

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Project description:ObjectiveExercise is a critical component of a healthy lifestyle and a key strategy for the prevention and management of metabolic disease. Identifying molecular mechanisms underlying adaptation in response to chronic physical activity is of critical interest in metabolic physiology. Circadian rhythms broadly modulate metabolism, including muscle substrate utilization and exercise capacity. Here, we define the molecular and physiological changes induced across the daily cycle by voluntary low intensity daily exercise.MethodsWildtype C57BL6/J male and female mice were housed with or without access to a running wheel for six weeks. Maximum running speed was measured at four different zeitgeber times (ZTs, hours after lights on) using either electrical or manual stimulation to motivate continued running on a motorized treadmill. RNA isolated from plantaris muscles at six ZTs was sequenced to establish the impact of daily activity on genome-wide transcription. Patterns of gene expression were analyzed using Gene Set Enrichment Analysis (GSEA) and Detection of Differential Rhythmicity (DODR). Blood glucose, lactate, and ketones, and muscle and liver glycogen were measured before and after exercise.ResultsWe demonstrate that the use of mild electrical shocks to motivate running negatively impacts maximum running speed in mice, and describe a manual method to motivate running in rodent exercise studies. Using this method, we show that time of day influences the increase in exercise capacity afforded by six weeks of voluntary wheel running: when maximum running speed is measured at the beginning of the nighttime active period in mice, there is no measurable benefit from a history of daily voluntary running, while maximum increase in performance occurs at the end of the night. We show that daily voluntary exercise dramatically remodels the murine muscle circadian transcriptome. Finally, we describe daily rhythms in carbohydrate metabolism associated with the time-dependent response to moderate daily exercise in mice.ConclusionsCollectively, these data indicate that chronic nighttime physical activity dramatically remodels daily rhythms of murine muscle gene expression, which in turn support daily fluctuations in exercise performance.

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Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle.

Publications

Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle.

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