Exercising late in the day benefits health and reduces weight – in mice

Diet and lifestyle 9. feb 2023 3 min Postdoc Milena Schönke Written by Morten Busch

Circadian rhythms influence almost everything in our bodies. Previous research has shown that the timing of exercise influences muscle building. Now researchers have examined more closely how this timing influences the metabolism of mice and thus potentially their weight and the risk of cardiovascular disease. They found that early exercise had no effect, whereas late exercise reduced fat mass by 19% and early signs of atherosclerosis. Interestingly, late exercise also increased the quantity of gut bacteria producing anti-inflammatory fatty acids. The researchers are now searching for the causes and for similar patterns among people to improve future treatment and prevention.

Whether you enjoy exercise or not, most people want to optimise its health benefits. Should you kickstart your day with a 5-km run or wrap it up with some strenuous exercise at the gym after a long workday? Exercise performance has long been known to peak in the evening, but whether this is also the best time to maximise benefits for health and weight remains unclear. A new study examined more closely whether the timing of exercise is associated with the development of cardiometabolic diseases in mice.

“People have many opinions on this topic that are not always backed up scientifically. We found that late exercise significantly reduced weight and the size of early-stage atherosclerotic lesions. The gut microbiota of the mice exercising late also changed notably. We do not yet know whether this is coincidental or causal. We will now try to translate these studies to people to determine whether they have an optimal time to exercise so that we can improve how exercise affects prevention and treatment,” explains Milena Schönke, Postdoctoral Fellow, Department of Medicine, Leiden University Medical Center, Netherlands.

Studying people is difficult

Many years ago, researchers demonstrated that circadian rhythm strongly influences the regulation of many organisms. The timing of exercise matters. Thus, a few years ago researchers found that the molecular fingerprint of exercise in muscles changes depending on when it is performed. Based on this, Milena Schönke’s team hypothesised that the timing of exercise probably also affects health.

“We therefore decided to study this, first for atherosclerosis, and we know fairly well what modulates it. The idea is that the timing of exercise influences how it affects the body – depending on the time of day and then also linked to meal times. So, jumping out of bed and running affects metabolism differently than running later,” says Milena Schönke.

Studying how people develop atherosclerosis is difficult since it develops slowly over years or even decades, so researchers therefore typically use various mice with specific traits.

“These mice tend to develop high levels of serum cholesterol and then develop atherosclerotic lesions in the artery walls. There are several similar mouse models, but we decided to use this one, since their cholesterol metabolism is closest to that of humans, with the cholesterol shuffling back and forth between the liver and the periphery,” explains Milena Schönke.

Gut microbiota among marathon runners

The researchers only had to exercise the mice for weeks to begin to see signs and changes – instead of people having to exercise for years. For 4 weeks, 5 days a week, the researchers put the mice on a treadmill for 1 hour – either in the early or late active phase of their day.

“Mice are nocturnal, so we do all experiments during the night when they are active. They wake up when it gets dark, so early means early in the dark phase and late means at the end of the dark phase. Many people get confused about that,” says Milena Schönke.

The results were clear. Late but not early exercise training reduced fat mass by 19% and the size of early-stage atherosclerotic lesions by as much as 29% versus animals not exercising. Surprisingly, early exercise training had no benefits. One possible explanation for the positive effect of late exercise was the composition of the gut microbiota.

“Strikingly, the time of exercise affected the composition of the gut microbiota. Late exercise promoted the enrichment of gut bacteria that produce short-chain fatty acids and have thereby been proposed to have anti-inflammatory properties,” explains Milena Schönke.

Previous studies have shown that exercise influences the gut microbiota of marathon runners, but since their gut bacteria differ from those of untrained people, the researchers were not sure whether they would find a similar effect.

“Future studies can identify the role of the gut microbiota in this effect. We must also further characterise the molecular changes within the atherosclerotic lesions to understand whether the bacteria are the cause the of the improved health,” says Milena Schönke.

Would greatly enhance efficacy

Exercise training has long been known to improve cardiometabolic health, but this is the first time research has demonstrated that exercising at different times influences the development of weight and atherosclerosis – at least in mice. Now, that this has been shown in mice, the goal is to translate this to humans.

“We are about to start a clinical study involving people, not on the cardiovascular aspect, because atherosclerosis develops slowly. Instead, we will study the liver, because people can reduce liver fat quite rapidly, but no drugs can specifically reduce liver fat, so we hope that the timing of exercise can have an effect,” explains Milena Schönke.

The researchers also plan to investigate whether gut bacteria influence the beneficial effects and to combine the exercise with boosting dietary fibre to study how this affects the gut microbiota.

“These findings in mice indicate that timing is critical to the beneficial anti-atherosclerotic effects of exercise, so we think that there is great potential to further optimise the exercise training recommendations for people,” says Milena Schönke.

Cardiovascular disease remains the leading cause of death worldwide, taking nearly 18 million lives each year. An active lifestyle with regular exercise is a cornerstone of prevention. Identifying the optimal time to exercise would greatly enhance the efficacy of exercise programmes.

“We definitely need to improve our recommendations. If exercising late turns out to be the best time and if you can tell people specifically that they should do this, then this motivates them more easily since they get results more rapidly and this increases the effect of whatever exercise they can manage. And this can also potentially reduce the need for drug treatment and the number of individuals becoming ill in the first place,” concludes Milena Schönke.

Time to run: late rather than early exercise training in mice remodels the gut microbiome and reduces atherosclerosis development” has been published in The FASEB Journal. In 2018, the Novo Nordisk Foundation awarded a postdoctoral fellowship to Milena Schönke for the project Running from Cardiometabolic Disease: Role of Lipoprotein Metabolism and the Timing of Exercise.

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