Exercise in the morning or in the evening has a completely distinct effect!

Life is all about working out. Moderate exercise not only strengthens the body, but also improves the metabolic state and slows the progression of diseases. However, different times of exercise may have different impacts, and it is an intriguing scientific question how to determine the best time to exercise.

Although the influence of exercise on energy metabolism is well recognized, there is still a lack of study on how exercise timing affects metabolic state, and we are still unaware of the similarities and differences between different exercise time periods.

This question is answered in a recent publication published in Cell Metabolism. Researchers discovered, using a mouse model, that exercise at different times of the day has varied impacts on local and systemic metabolism.

The mice were placed into two experimental groups: one that exercised on a treadmill for an hour in the early morning (early light) or evening (early dark), and one that did not.

Following the exercise, tissues from various parts of the mice were collected, including serum, skeletal muscle, liver, epididymal white adipose tissue (eWAT), inguinal subcutaneous white adipose tissue (iWAT), and interscapular brown adipose tissue (BAT), and the metabolites and gene expression status of these tissues were histologically analyzed.

Each tissue displayed a distinct metabolic response depending on the time of exercise. Activity in the evening altered 197 metabolites in muscle tissue, while exercise in the early morning altered 52 metabolites, for a total of 31 metabolites altered by exercise at both times.

In the liver, 129 and 143 metabolites altered in the early morning and evening, respectively, while 101 metabolites changed in both. In eWAT, metabolites are often lower after early morning activity but higher after late exercise. As a result, researchers came to the conclusion that the effect of exercise on metabolites is time-dependent and tissue-specific.

Evening exercise had a greater impact on amino acids and lipids when evaluated by metabolite class. Early morning exercise elevated corticosterone levels in muscle, heart, eWAT, iWAT, and BAT. After early morning activity, hepatic maltopentaose, maltotetraose, and maltotriose reduced the greatest, while glucose declined in the evening.

Furthermore, exercise elevated corticosterone levels in all tissues, although the highest levels of liver and muscle corticosterone were detected following early morning activity. Evening exercise increases ketones from ammonia detoxification metabolism, such as beta-hydroxybutyric acid and urea.

The altered metabolites were also subjected to genetic testing and KEGG enrichment analysis by the research team. They discovered that following early morning exercise, the liver demonstrated a considerable fatty acid metabolic response, with selective increases in fatty acid metabolites. Furthermore, glucose metabolism in the liver was increased during early morning activity, indicating that hepatic glycogen is a preferentially utilized raw material during early morning exercise.

Early morning exercise lowered liver glycogen levels in terms of glucose metabolism. Simultaneously, genes involved in glycolysis in muscles were upregulated after nighttime exercise. The researchers said that energy provided by glycogenolysis and gluconeogenesis in the liver is sufficient for exercise in the early morning, but in the evening, the liver's generation of glucose may be limited, resulting in the body's increased reliance on muscle glycogen.

In terms of amino acid metabolism, amino acids were found to be substantially concentrated in the blood of mice that exercised in the evening, indicating enhanced protein breakdown and amino acid use following evening exercise. Muscle glycine, serine, threonine, lysine, and tyrosine levels increased in response to evening activity, but not in response to early morning exercise.

While levels of glycine, serine, threonine, and phenylalanine metabolism increased in the liver following evening activity, the liver also showed enrichment in amino acid metabolic pathways following early morning exercise. According to the researchers, this indicates that the liver can dynamically control and utilize amino acid metabolism depending on the time of activity.

In terms of lipid metabolism, early morning activity significantly increased a fraction of fatty acids in the liver, whereas evening exercise increased fatty acids in the serum, eWAT, and iWAT. Glycerol in the liver increased considerably following early morning activity, but glycerol in the iWAT increased following nighttime exercise. The researchers explained that early morning exercise stimulates lipolysis in the liver, but evening exercise stimulates lipolysis in the iWAT.

After evening exercise, acylcarnitine levels in muscle increased, indicating that evening exercise triggered fat oxidation in muscle and created a more robust need for energy sources other than glycolysis than early morning exercise.

Overall, it appears that exercise in the early morning and late evening has its own metabolic consequences. Early morning exercise provides energy mostly via the glucose metabolic pathway; liver glycogen reserves are more abundant, less prone to big variations in blood sugar, and may be better acceptable for people with glucose metabolism disorders, such as diabetes and hypoglycemia patients. Evening exercise mobilizes more lipolysis, which may be more appropriate for people who are trying to lose weight. However, protein breakdown is more severe in the evening when exercising, so protein-based nutrition must be supplemented on a regular basis.

The researchers also noted the study's limitations, such as the fact that mice's circadian pattern is diametrically opposed to that of humans, which may interfere with the generalizability of the findings. Furthermore, the article did not examine the impact of various exercise styles on metabolism, and the conclusions may not be applicable to all types of exercisers.

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