Circadian RythmsMetabolismSleep

All in good time – the effects of circadian rhythms on exercise efficiency and metabolic disease.


– PhD

Affiliations : Group Leader at EMBL

Journal reference: DOI: 10.1038/s41574-018-0150-x

Summary: Our circadian rhythms and physical activity levels are modulated by our metabolism. In her article Dr. Bošković explores the balance of rest and acitivty on our metabolism and the potential therapeutic advantages resulting from the synergy of these two systems.

Metabolic diseases, such as Type 2 Diabetes and Obesity, represent a major global health concern. As of 2018, it is estimated that over a billion people worldwide are affected by some form of metabolic abnormality, including insulin resistance, elevated blood pressure and abnormally high concentration of fats in the blood. Modern lifestyle, characterized by unhealthy eating and resting habits, exposure to artificial light and stress, together with genetic predisposition, represent important contributors in metabolic disease onset and progression. In their Review, Gabriel and Zierath discuss the intriguing interplay between oscillating daily cycles of activity and rest – known as circadian rhythms – and exercise timing in metabolic output and physiology. 

On both an organismal and cellular level, circadian clocks can regulate metabolic processes. The core clock, localized in the brain, synchronizes, maintains and modulates the rhythms of peripheral clocks, and is informed by various internal and external Zeitgebers (German: time-giver, synchronizer), such as body temperature, light, nutrients, etc. Molecularly, the key clock genes are transcriptional activators CLOCK and BMAL1 (and their targets), which through negative feedback loop regulate various aspects of cell’s function. 

In this Review, the authors report on studies from animal models and humans indicating that the disruption of the circadian rhythm machinery (in the brain as well as throughout the body) is highly detrimental to metabolism and can result in insulin resistance and obesity. For instance, in both naturally occurring genetic variants and experimentally perturbed systems, disruptions in circadian clock machinery of skeletal muscle cells negatively impact muscle cell metabolism, resulting in reduced insulin-mediated glucose uptake and mitochondrial respiration.

It is both intuitive and documented that exercise is beneficial for a person’s physiology. Regular exercise of moderate and high intensity can positively affect insulin sensitivity and glucose metabolism. In recent years, mounting experimental evidence indicates that exercise functionally interacts with the molecular clock: physical activity can modulate the amplitude and phase of the cellular circadian clock, and the output and efficiency of exercise depends on the status of the circadian machinery in cells. For example, exercise was shown to induce gene expression changes of clock genes in a muscle undergoing training, compared to the resting muscle. Conversely, peak performance during resistance exercise and high intensity training is observed between 4 and 8 PM, with the lowest between 6 and 10 AM. The authors note that these observations could, at least partially, be explained by the daily shifts in body temperature / heat dissipation efficiency – we are, on average, ~0.8°C warmer in the afternoon compared to the morning, and the core clock machinery in the skeletal muscles is strongly susceptible to temperature synchronization. Furthermore, other factors, such as hormonal fluctuations or chronotype – whether you are a morning or an evening person, activity-wise – could contribute to the molecular response to exercise. 

Interestingly, acute and long-term exercising before 10 PM has been reported to boost the quality of sleep – a finding that could be particularly beneficial for people working night-shifts, as these individuals can develop irregular sleeping patterns and are also increasingly at risk of developing metabolic diseases.  Therefore, using exercise to retain normal circadian rhythms could improve sleep quality and aid in adapting to shift-work, combating sleep deprivation. 

Human physiology is highly adaptive to its environment; it is, therefore, difficult to disentangle the relative contribution of various inputs shaping our metabolism and health. Currently, we do not have an in-depth understanding of the role of circadian timing in maximizing the health benefits of physical activity, although this field of research will undoubtedly expand in the coming years. Nevertheless, the conspicuous link between the circadian rhythms and exercise training provide an attractive possibility that by synchronizing the optimal exercise and rest timing with one’s internal clock could open new and synergistic therapeutic avenues towards amelioration or even prevention of metabolic diseases. 

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