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. 2017 Jan;132:161-165.
doi: 10.1016/j.biochi.2016.11.014. Epub 2016 Dec 2.

Homeostatic Effects of Exercise and Sleep on Metabolic Processes in Mice With an Overexpressed Skeletal Muscle Clock

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Free PMC article

Homeostatic Effects of Exercise and Sleep on Metabolic Processes in Mice With an Overexpressed Skeletal Muscle Clock

Allison J Brager et al. Biochimie. .
Free PMC article

Abstract

Brain and muscle-ARNT-like factor (Bmal1/BMAL1) is an essential transcriptional/translational factor of circadian clocks. Loss of function of Bmal1/BMAL1 is highly disruptive to physiological and behavioral processes. In light of these previous findings, we examined if transgenic overexpression of Bmal1/BMAL1 in skeletal muscle could alter metabolic processes. First, we characterized in vivo and ex vivo metabolic phenotypes of muscle overexpressed mice (male and female) compared to wild-type littermates (WT). Second, we examined in vivo and ex vivo metabolic processes in the presence of positive and negative homeostatic challenges: high-intensity treadmill running (positive) and acute sleep deprivation (negative). In vivo measures of metabolic processes included body composition, respiratory exchange ratio (RER; VCO2/VO2), energy expenditure, total activity counts, and food intake collected from small animal indirect calorimetry. Ex vivo measure of insulin sensitivity in skeletal muscle was determined from radioassays. RER was lower for muscle overexpressed females compared to female WTs. There were no genotype-dependent differences in metabolic phenotypes for males. With homeostatic challenges, muscle overexpressed mice had lower energy expenditure after high-intensity treadmill running. Acute sleep deprivation reduced insulin sensitivity in skeletal muscle in overexpressed male mice, but not male WTs. The present study contributes to a body of evidence showing pleiotropic, non-circadian, and homeostatic effects of altered Bmal1/BMAL1 expression on metabolic processes, demonstrating a critical need to further investigate the broad and complex actions of Bmal1/BMAL1 on physiology and behavior.

Keywords: Insulin sensitivity; Molecular circadian clock; Resting energy expenditure; Restricted sleep; Treadmill running; VO(2) max.

Conflict of interest statement

Statement: The authors have indicated no financial conflicts of interest.

Figures

Figure 1
Figure 1. Dose response curve of insulin-stimulated glucose uptake in soleus muscle
Soleus muscle extracted at midday was stimulated with insulin and subjected to radioassay analyses with 2-deoxy-d-[1,2-3H]glucose (1.5 mCi/ml) and 7 mM d-[14C]mannitol. Means±SEM % change in the extent of glucose uptake (nmol/ml) in stimulated versus unstimulated muscle extracted from the same mouse. *SOD, sub-optimal dose.
Figure 2
Figure 2. Negative homeostatic (sleep) challenge reduces insulin sensitivity in skeletal muscle of mice with muscle-specific clock gene overexpression
Mice were left undisturbed or had been gently handled for 6 h in their home cages immediately prior to muscle extraction at midday. Means±SEM % change in the extent of glucose uptake (nmol/ml) in stimulated versus unstimulated muscle extracted from the same mouse. a*, p<0.05; two-way ANOVA.

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