Effect of exercise varies according to the time of day

Diet and lifestyle 22. feb 2022 3 min Scientific Director, Professor Juleen Zierath Written by Kristian Sjøgren

The body responds differently to exercise depending on the time of day. Researchers have produced an atlas of how it affects organs and tissues, weight loss and controlling blood glucose, such as in type 2 diabetes.

In a new study on mice, researchers created an atlas of how exercise affects all tissues and organs differently at different times of the day.

The atlas may influence the recommended time of day people should exercise if they have type 2 diabetes or want to lose weight.

In addition, an improved understanding of how the time of day affects the benefits of exercise may have pharmaceutical potential.

“Finding the metabolites that respond differently to exercise depending on the time of day would enable us to better understand their role in healthy metabolism. The metabolites can be used as tissue-specific biomarkers to improve understanding of how to maintain health or might be used as dietary supplements if they promote health,” explains the leader of the study, Juleen R. Zierath, Professor, Karolinska Institutet, Stockholm, Sweden and Executive Director, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

The research has been published in Cell Metabolism.

Circadian rhythm regulates life

Juleen R. Zierath’s research focuses on the circadian rhythm and how it improves or worsens health by orchestrating rhythmic biological processes.

Almost all human cells have a circadian rhythm. During an approximately 24-hour cycle, the body carefully regulates the concentrations of various hormones and signalling molecules and how genes are expressed, and this affects metabolism, blood pressure, sleep, liver function, hunger, energy and much more.

The BMAL1, CLOCK and PER3 clock genes are key to setting the circadian rhythm and are similar to a circuit-breaker. If these genes are disabled experimentally, animals lose their circadian rhythm and their hormones and metabolism and patterns of sleeping and eating become arbitrary.

People with mutations in their clock genes have no normal circadian rhythm and often have mood swings.

A poorly regulated circadian rhythm is associated with a higher risk of becoming overweight or developing metabolic disorders such as type 2 diabetes, such as among people who work at night and people who often have jet lag.

In the new study, the international research team aimed to produce an atlas of how the circadian rhythm affects the benefits of exercise.

Mice ran at different times

The researchers persuaded mice to run on a treadmill for 1 hour at different times of the day.

  • Some mice exercised in the early active phase of the day, equivalent to early morning for people.
  • Some mice exercised in the early rest phase, equivalent to waking right after falling asleep and then running.
  • Some mice did not exercise at all.

After the exercise, the researchers took tissue samples from all organs, including the liver, heart, kidneys, lungs, brain, blood, brown fat and other fat tissue.

The researchers applied global metabolomic profiling to the tissue samples to measure the concentrations of all metabolites, including proteins, signalling molecules and other markers, to determine how they responded to exercise at various times of the day.

Exercise has more benefits during daylight hours

The research resulted in a comprehensive atlas of how exercise affects the metabolomic profile of all tissues at different times of the day.

The results show that early-morning exercise caused a greater metabolic response than exercise at night.

Juleen R. Zierath says that exercise did not change the metabolomic profile of some organs at all during the resting phase (nighttime) compared with non-exercising mice.

“All our cells have an internal clock that controls the transcription of thousands of genes related to metabolism. The hormones also fluctuate during the day, and this can affect the expression of genes, which in turn affects metabolism. This is why the time of day you exercise may differentially affect the metabolomic profile,” says Juleen R. Zierath.

Circadian rhythm should determine the timing of exercise

So how could people use this information?

According to Juleen R. Zierath, this depends on the purpose of exercise.

If you want to get laboratory mice to lose weight, persuade them to exercise in the early morning, because this boosts energy metabolism.

The body burns more fat if you exercise when the metabolism is at full speed versus exercising when the body wants to sleep.

“One implication could be on weight loss or blood glucose control. But the study also advances knowledge on how exercise affects various organs and the differences among these organs, including the heart, liver, brain and others,” explains Juleen R. Zierath.

Exercise in the active phase of the circadian cycle produced a greater correlation between the metabolomic profile in muscles and the liver, and this supports optimal glucose metabolism.

The researchers also suggested which biomolecules facilitate communication between the muscles and the liver.

“This insight may therefore also influence the understanding of how the interaction between exercise and the circadian rhythm can affect people with type 2 diabetes. Depending on the time of day, exercise may have different effects on controlling blood glucose. This may also affect our understanding of when exercise has the most benefits, depending on whether you are a night owl or a morning lark or some other chronotype,” concludes Juleen R. Zierath.

Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis” has been published in Cell Metabolism. Several authors are affiliated with the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

Juleen Zierath's research focuses on cellular mechanisms underlying the development of insulin resistance in Type 2 Diabetes (T2DM). The overarching...

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