Research in mice shows that time of day affects the effectiveness of exercise, but applying these results to humans is complicated.
Scientists already know that the circadian rhythm interacts with our metabolism. A person’s circadian rhythm includes physical, mental, and behavioral changes that follow a cycle of 24 hours.
These behavioral patterns develop in response to light and darkness and relate to the circadian clock, which follows the solar time. Circadian rhythms are present in most living things.
Two teams of researchers decided to explore how the time of day can affect the body’s response to exercise.
Gad Asher, who works in the Department of Biomolecular Sciences at the Weizmann Institute of Science in Rehovot, Israel, is senior author of the first study, while Paolo Sassone-Corsi of the Center for Epigenetics and Metabolism at the University of California (UC), Irvine, is senior author of the second.
“It’s quite well known that almost every aspect of our physiology and metabolism is dictated by the circadian clock,” notes Asher.
“Previous studies from our lab have suggested that at least 50% of our metabolism is circadian, and 50% of the metabolites in our body oscillate based on the circadian cycle. It makes sense that exercise would be one of the things that’s impacted,” says Sassone-Corsi.
Examining mice’s response to exercise
The two studies confirm that the circadian rhythm plays an essential role in the way that the body responds to physical movement. Although each team investigated a different component of exercise, the two studies complement each other.
Both teams explored the link between the time of day and exercise performance in mice. These creatures are nocturnal, so to make the results relatable to humans, the researchers had to focus on the active and resting phases of the mice rather than the time on the clock.
In the first study, the results of which feature in Cell Metabolism, Asher and team compared the exercise performance of mice at different times of the day by putting them in treadmills during their active phase. The mice performed better in the later stages of this phase, meaning that the “mouse evening” was a better time for them to exercise.
In the mouse evening, levels of a compound called 5-aminoimidazole-4-carboxamide ribonucleotide (ZMP) were higher. ZMP is necessary for metabolism because it activates metabolic pathways that lead to the breakdown of glucose and fatty acids.
This breakdown relies on the activation of AMPK, a master cellular metabolic regulator. The study findings suggest that ZMP may play a part in increasing exercise capacity in the evening.
“Interestingly, ZMP is an endogenous analog of AICAR (aminoimidazole carboxamide riboside), a compound that some athletes use for doping,” says Asher.
The researchers built on their findings by analyzing exercise performance in 12 humans. Using oxygen consumption as a measure of exercise efficiency, they concluded that the participants also had better exercise performance in the evening than in the morning.
Studying how exercise changes muscle
Sassone-Corsi and team also evaluated the performance of mice on treadmills, but they focused on the changes that exercise produced in the mice’s muscle tissue. Their results also appear in Cell Metabolism.
In taking this approach, they were able to investigate further the process that leads to glucose breakdown and lipid oxidation (fat-burning).
The findings showed that exercise activates a protein called hypoxia-inducible factor 1-alpha (HIF-1α) in different ways at different times of the day. HIF-1α responds to changes in oxygen levels in the body tissue by stimulating certain genes.
“It makes sense that HIF-1α would be important here, but until now, we didn’t know that its levels fluctuate based on the time of day,” says Sassone-Corsi.
Based on their findings, the researchers concluded that exercise has a more beneficial effect on the metabolism at the beginning of the mice’s active phase than toward the end. Translating this to human time, the effect was most positive in the late morning.
However, it is important to keep in mind that both studies used mice and that translating the findings to humans may be complicated because behavioral patterns vary greatly from person to person.
“You may be a morning person, or you may be a night person, and those things have to be taken into account,” concludes Sassone-Corsi.