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Circadian rhythms and exercise — re-setting the clock in metabolic disease

Abstract

Perturbed diurnal rhythms are becoming increasingly evident as deleterious events in the pathology of metabolic diseases. Exercise is well characterized as a crucial intervention in the prevention and treatment of individuals with metabolic diseases. Little is known, however, regarding optimizing the timing of exercise bouts in order to maximize their health benefits. Furthermore, exercise is a potent modulator of skeletal muscle metabolism, and it is clear that skeletal muscle has a strong circadian profile. In humans, mitochondrial function peaks in the late afternoon, and the circadian clock might be inherently impaired in myotubes from patients with metabolic disease. Timing exercise bouts to coordinate with an individual’s circadian rhythms might be an efficacious strategy to optimize the health benefits of exercise. The role of exercise as a Zeitgeber can also be used as a tool in combating metabolic disease. Shift work is known to induce acute insulin resistance, and appropriately timed exercise might improve health markers in shift workers who are at risk of metabolic disease. In this Review, we discuss the literature regarding diurnal skeletal muscle metabolism and the interaction with exercise bouts at different times of the day to combat metabolic disease.

Key points

  • Skeletal muscle has an extensive network of clock-controlled genes, and dysregulation of its molecular clock can lead to deleterious metabolic consequences.

  • Physical strength and skeletal muscle mitochondrial function peak in the late afternoon, whereas low-energy sensitive signalling peaks in the morning.

  • Exercise is a robust Zeitgeber of skeletal muscle clocks, and exercise can reset the molecular circadian clock, thereby effectively ameliorating the negative effects of disrupted sleep patterns.

  • Optimizing the timing of exercise bouts could aid existing therapeutic interventions for the management of metabolic disease.

  • Divergent modalities of exercise can interact with the circadian rhythm, resulting in potent metabolic effects.

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Fig. 1: Skeletal muscle biology and the core clock.
Fig. 2: Human skeletal muscle circadian biology.

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Acknowledgements

The authors are supported by grants from the Novo Nordisk Foundation (NNF14OC0011493, NNF14OC0009941 and NNF18CC0034900), the Wenner-Gren Foundation, the Swedish Research Council (2015–00165), the European Research Council (233285) and the Strategic Research Programme in Diabetes at Karolinska Institutet (2009–1068). The authors are grateful to B. Atkins for his contribution to figure design.

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B.M.G. and J.R.Z. contributed equally to all aspects of the article.

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Correspondence to Juleen R. Zierath.

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Glossary

Core clock

A set of protein-coding genes (active in nearly all mammalian cells) that oscillate in expression and activity in a circadian manner.

Training

Repeated bouts of exercise resulting in physiological adaptations.

Diurnal

A diurnal cycle is any pattern that recurs every 24 hours, not necessarily biological or intrinsic.

Zeitgeber

A rhythmically occurring natural phenomenon that acts as a cue in the regulation of the body’s circadian rhythms.

Oxygen consumption rate

The amount of oxygen consumed by metabolic processes in tissues, cells or organelles. When applied to measuring mitochondria, different metabolic states (states 1–5) of the mitochondria are used.

Chronotype

The interindividual differences in the circadian phase of activity patterns and sleep–wake cycles.

Maximal power output

Maximal intensity of exercise or skeletal muscle contraction measured by power output (Watts).

Maximal sprint

A short burst of intense exercise after which the individual is momentarily unable to continue owing to fatigue.

Cycle ergometer

A fixed cycling machine often used in fitness testing to estimate exercise intensity.

Periodized nutrition

The strategic combined use of exercise training and nutrition, or nutrition alone, with the overall aim to improve the physiological response to exercise training.

Voluntary muscle force

Skeletal muscle contraction force produced as a result of endogenous activation of motor neurons.

Acute exercise

A single exercise bout, rather than exercise training.

Sleep hygiene

Habits and practices that are conducive to sleeping well on a regular basis.

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Gabriel, B.M., Zierath, J.R. Circadian rhythms and exercise — re-setting the clock in metabolic disease. Nat Rev Endocrinol 15, 197–206 (2019). https://doi.org/10.1038/s41574-018-0150-x

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