Homeostatic effects of exercise and sleep on metabolic processes in mice with an overexpressed skeletal muscle clock

Dec 6, 2016Biochimie

How Exercise and Sleep Balance Metabolism in Mice with an Overactive Muscle Body Clock

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Abstract

Muscle overexpressed females showed a lower respiratory exchange ratio compared to wild-type counterparts.

Transgenic overexpression of Bmal1/BMAL1 in skeletal muscle may influence metabolic processes.
No significant differences in metabolic phenotypes were observed in male mice with Bmal1/BMAL1 overexpression.
Muscle overexpressed mice displayed lower energy expenditure following high-intensity treadmill running.
Sleep deprivation was associated with reduced insulin sensitivity in skeletal muscle of overexpressed male mice, in contrast to wild-type males.
The findings suggest complex, non-circadian effects of Bmal1/BMAL1 on metabolism.

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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; VCO/VO), 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. 2 2

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Homeostatic effects of exercise and sleep on metabolic processes in mice with an overexpressed skeletal muscle clock

Abstract

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