What Are Exerkines? How Exercise Signals Between Organs

Exercise does much more than make your muscles work harder. It changes the chemistry of your blood and sends signals throughout your body.

Many of those signals are called exerkines. They are molecules released or changed in response to exercise that can help cells and organs communicate with one another.

Some come from working muscles. Others come from the liver, fat, heart, brain, immune system, and other tissues. Together, they may help explain how physical activity can affect so many parts of the body at once, from blood sugar and heart health to brain function and the immune system. [1]

Scientists are still learning which exerkines matter most, where they come from, and exactly what they do. Some findings are well supported in humans. Others come mainly from mice or cells grown in a laboratory.

That makes exerkines one of the most promising, and sometimes confusing, areas of exercise research.

Exerkines At a Glance

• What they are: Molecules that help carry biological signals during or after exercise
• Where they come from: Muscle, fat, liver, heart, brain, immune cells, bone, and other tissues
• What they include: Proteins, hormones, small metabolites, fats, and pieces of genetic material such as RNA
• What they may affect: Metabolism, inflammation, blood vessels, muscles, the brain, and the immune system
• Do all workouts produce the same exerkines? No. The response can change with exercise type, intensity, duration, fitness, diet, age, and other factors
• Can exerkines replace exercise? No. Scientists are studying whether some could someday lead to treatments, but there is no “exercise pill” that can copy everything exercise does

What Exactly Is an Exerkine?

An exerkine is not one particular hormone or protein. It is a broad name for biological signals connected with exercise.

A major review in Nature Reviews Endocrinology defines exerkines as signaling molecules released in response to a single workout or to repeated exercise training. These signals can act on the cell that released them, on nearby cells, or on tissues elsewhere in the body. [1]

That last part is important.

Imagine a muscle contracting during a run. The muscle does not simply use energy and produce force. It can also release molecules that enter the blood. Those molecules may then influence fat, the liver, blood vessels, immune cells, or even the brain.

Exercise therefore creates a conversation among organs.

Exerkines are some of the messages.

Are Exerkines the Same as Myokines?

Not quite.

A myokine is a signaling molecule released by muscle. Some myokines are also exerkines because exercise changes their production or release.

But exerkines do not have to come from muscle.

Scientists have identified exercise-linked signals from many tissues. Liver signals are sometimes called hepatokines. Signals from fat are called adipokines. The heart can release cardiokines, while the nervous system can produce neurokines. [1]

So “myokine” tells you where a signal came from.

“Exerkine” tells you that the signal is part of the body’s response to exercise.

What Kinds of Molecules Can Be Exerkines?

Exerkines come in many forms.

Some are proteins or small protein-like molecules called peptides. Others are hormones, fats, or metabolites, which are small chemicals produced as cells use and process energy.

Some exerkines are pieces of genetic material, including small forms of RNA that can affect how genes behave. [1]

A 2024 review in Biomedicines described exerkines as a broad family that can include hormones, proteins, peptides, metabolites, and nucleic acids. [2]

This means there is no single “exerkine system” in the way there is an insulin system or thyroid hormone system.

The term describes a huge network of signals that change as the body responds to physical activity.

How Do Exerkines Travel Around the Body?

Some exerkines enter the bloodstream and travel to distant organs.

Others act close to where they were released.

Scientists use three terms for these different kinds of signaling:

Endocrine signaling means a molecule travels through the blood and affects another part of the body.

Paracrine signaling means it acts mainly on nearby cells.

Autocrine signaling means a cell releases a signal that acts back on the same cell.

Exerkines can work in any of these ways. [1]

The bloodstream therefore matters, but it is not the whole story. Some important exercise signals may never travel very far from the tissue that produced them.

What Are Extracellular Vesicles?

Some exercise signals may travel inside tiny packages called extracellular vesicles.

These are very small bubbles surrounded by a thin membrane. Cells release them into their surroundings, including the bloodstream.

Inside, the vesicles can carry proteins, fats, and genetic material such as RNA. Other cells can take up these packages and respond to what is inside. [1]

Scientists are increasingly interested in extracellular vesicles because they could help explain how one organ sends detailed instructions to another during exercise.

But studying them is difficult. They are tiny, their contents vary, and separating them from all the other material in blood requires careful laboratory methods.

How Did Scientists Discover Exerkines?

One of the key discoveries came from a molecule called interleukin-6, or IL-6.

IL-6 was already known as part of the immune system. But in 2000, researchers showed that contracting human muscles could produce and release large amounts of IL-6 during exercise.

That helped establish a new idea: skeletal muscle was not simply machinery for movement. It could also behave like a signaling organ. [1]

IL-6 became one of the first well-known myokines.

Researchers soon began finding many more exercise-linked molecules. Attention also moved beyond muscle as scientists discovered that exercise changes signals coming from fat, the liver, heart, immune system, brain, and other tissues.

The word “exerkine” gave researchers a way to talk about this larger communication network.

Why Is Muscle So Important?

Muscle remains a major part of the story because a large amount of tissue becomes active during exercise.

When muscles contract, they rapidly use fuel, change their demand for oxygen, and alter their internal chemistry. They also send signals to other parts of the body.

Those signals can help coordinate the body’s response.

A working muscle may need more fuel from fat stores. The liver may need to help maintain blood glucose. Blood vessels must deliver more oxygen. The immune system responds to the physical stress of exercise. The brain must control movement while also monitoring temperature, energy, and fatigue.

Exerkines are one way these different systems can coordinate their work.

But modern exerkine research has moved away from the idea that muscle alone directs the response. Exercise is a whole-body event, and many organs appear to both send and receive molecular signals.[1]

Does Exercise Intensity Change Exerkines?

Yes, and researchers are beginning to see just how large the difference can be.

A 2026 study in Cell Reports Medicine compared molecular changes after different kinds of exercise.

In one experiment, participants performed six 30-second all-out cycling sprints, for about three minutes of total sprinting. Researchers compared their blood with samples taken after much longer sessions of moderate exercise. [3]

The difference was striking.

The sprint session changed 714 of the 2,884 blood proteins measured immediately after exercise. Ninety minutes of moderate cycling changed only seven at that same point.

Sprinting also changed more than 200 metabolites.

Blood collected after the sprint session strongly changed gene activity when researchers exposed human fat cells to it in the laboratory. Blood collected after moderate cycling had a much smaller immediate effect. [3]

The study shows that exercise intensity can have a major effect on the molecular messages entering the bloodstream.

But it does not show that three minutes of sprinting is healthier than 90 minutes of moderate exercise.

The researchers measured molecular changes, not long-term health outcomes. The study groups were also small and mostly male. Most importantly, the sprint and moderate sessions differed in both intensity and duration, making it difficult to know which factor caused each difference. [3]

Can Exerkines Change How the Body Uses Energy?

This is one of the main areas scientists are studying.

Exercise forces tissues to quickly decide where fuel should come from and where it should go.

Muscles need energy. Fat tissue can release stored fatty acids. The liver helps control the supply of glucose. Hormones adjust how cells handle those fuels.

Exerkines may help coordinate some of these changes.

One example is 12,13-diHOME, a fat-related signaling molecule released from brown fat during exercise. Studies in humans and mice suggest that it can help skeletal muscle take up and burn fatty acids. [1]

Another example is lactate.

Lactate was once widely treated mainly as a waste product of hard exercise. Scientists now know it can also serve as fuel and as a biological signal.

Research in mice suggests that exercise-related lactate can affect fat cells and change the release of other signals involved in glucose and fat metabolism. Some related changes have also been observed in people. [1]

This illustrates why exerkine biology gets complicated quickly. One molecule can affect another tissue, which can then release another signal.

Exercise can start a chain of conversations.

Can Exerkines Affect the Brain?

They may be one reason exercise affects the brain, but much of this research is still developing.

Scientists have studied several possible links between exercise and brain signaling, including BDNF, irisin, cathepsin B, and other molecules.

BDNF, or brain-derived neurotrophic factor, helps support nerve cells and the brain’s ability to change and adapt. Exercise has been linked with changes in BDNF, although human studies have not always produced the same results. [1]

Animal research has also suggested that the muscle-linked molecule irisin can affect signaling in the hippocampus, a brain area important for learning and memory.

But evidence from mice should not automatically be treated as evidence that the same process works the same way in humans.

That distinction is especially important in exerkine research because many of the strongest experiments involve animals or cells grown in laboratories.

What Do Platelets Have to Do With Exercise?

One surprising clue came from platelets, tiny pieces of cells best known for helping blood clot.

A 2023 study in Nature Communications investigated how exercise affects the aging mouse brain.

Researchers found that platelets were involved in the increase in new neurons seen after exercise. They focused on a protein called platelet factor 4, or PF4, which is also known as CXCL4.

Exercise caused platelets to release PF4. When researchers gave PF4 to aged mice, the animals showed improvements in measures of brain cell growth and cognition. [4]

The finding is important because it shows how an exercise response outside the brain may influence what happens inside the brain.

But the experiment was done in mice.

It does not mean PF4 injections have been shown to improve memory in older people, and it does not mean PF4 can replace exercise. Human studies would be needed to determine whether the same pathway can be used safely or effectively.

Could Exerkines Matter in Parkinson’s Disease?

Scientists are also studying whether communication between muscle and the brain could matter in Parkinson’s disease.

A 2026 review in Neuroprotection examined 129 studies on exercise, muscle health, and Parkinson’s disease. [5]

The researchers discussed several possible muscle-to-brain signals, including BDNF, IGF-1, irisin, cathepsin B, myostatin, and GDF15. These molecules have been studied for possible roles in inflammation, energy use, brain plasticity, and the health of nerve cells.

Exercise itself can improve important outcomes for people with Parkinson’s disease, including strength, balance, walking, and quality of life.

But the exerkine part of the story is less certain.

The 2026 paper was a review of existing research, not a clinical trial showing that a particular exerkine can treat Parkinson’s disease. Scientists are still working out which muscle signals reach the brain, which ones matter most, and whether any can safely be turned into treatments.

Can Exerkines Affect the Immune System?

Exercise can cause short-term changes in inflammation and immune activity.

Some exerkines are themselves immune signals.

For example, IL-6 rises sharply during some forms of exercise. Other molecules, including IL-10 and IL-1 receptor antagonist, can also change after strenuous activity. [1]

This does not mean that exercise simply “boosts” the immune system.

Immune biology is more complicated than that.

A hard workout can produce a temporary stress and inflammatory response. The body then changes other signals as it recovers. Regular training can produce a different pattern from a single workout and is often associated with lower levels of chronic inflammation.

The timing of a blood sample therefore matters greatly when scientists study exerkines.

What Do Exerkines Have to Do With Cancer?

Cancer researchers are becoming interested in exercise as a way to discover biological pathways that tumors or immune cells might respond to.

A 2026 perspective in EXO – Beyond the Cell highlighted several examples. [6]

One involves lactate. Preclinical research suggests that exercise-related changes in lactate can alter the behavior of CD8+ T cells, immune cells that can attack cancer cells.

Other studies have examined muscle signals such as IL-15 and exercise-related changes in the gut microbiome.

The goal is not simply to prove that people with cancer should exercise. Researchers already study exercise itself as part of cancer care.

The newer question is whether exercise can serve as a discovery tool. If scientists can learn exactly which signals help the immune system or change tumor biology, some of those pathways might eventually lead to new treatments.

For now, much of this work is preclinical. Exerkines are not approved cancer treatments, and no single molecule can reproduce the many effects exercise has throughout the body.

Are Exerkines the Same After One Workout and Months of Training?

No.

This is one of the most important ideas in exerkine research.

A single workout can cause a burst of molecules that rise and fall over minutes or hours.

Regular training can change the body in a different way. It can alter resting metabolism, the number of receptors on cells, gene activity, muscle structure, blood vessels, and how strongly tissues react the next time a person exercises.

The level of an exerkine after one hard workout can therefore be very different from its level in a trained person who is resting.

In some cases, acute and long-term effects even seem to point in different directions. [1]

This is one reason scientists must be careful when saying that a molecule “goes up with exercise” or “goes down with exercise.”

The better question is: What kind of exercise, measured when, and in whom?

Why Do Different People Produce Different Exerkine Responses?

Two people can complete the same workout and show different biological responses.

Fitness is one reason. Age, sex, body composition, health, genetics, diet, sleep, medications, and previous exercise may also matter.

Even the time of day or whether someone recently ate can affect measurements. [1]

Researchers are interested in whether exerkine patterns could someday help explain why some people gain certain benefits from a training program more easily than others.

That could eventually contribute to more personalized exercise advice.

But scientists are not yet able to take a blood sample, measure a few exerkines, and reliably tell someone exactly how they should exercise.

That remains a research goal.

Is Every Molecule That Changes After Exercise an Exerkine?

Not necessarily.

Modern laboratory tools can measure thousands of proteins, fats, metabolites, and pieces of RNA at the same time. Exercise can change hundreds of them.

But seeing a molecule rise or fall does not prove that it is sending an important message.

The change could be a side effect of energy use, tissue stress, blood flow, cell damage, or another process.

To show that a molecule is acting as a meaningful exerkine, researchers ideally need to determine where it comes from, what causes its release, which cells receive it, and what happens when the signal is blocked or increased.

That kind of cause-and-effect evidence is still missing for many proposed exerkines.

This is one reason the Society for Endocrinology has cautioned that some claims about exerkines remain debated. [7]

Why Has “Omics” Research Become So Important?

Early exercise studies often measured one molecule at a time.

Today, researchers can examine thousands.

Proteomics measures proteins.

Metabolomics measures small molecules created by metabolism.

Lipidomics looks at fats and fat-related molecules.

Transcriptomics measures RNA and gene activity.

Scientists can combine these tools to watch the body respond to exercise across many biological systems at once.

In one earlier human study discussed in the Nature Reviews Endocrinology review, a single bout of exercise changed more than half of the molecules measured across several types of molecular data. [1]

The 2026 sprint study provides a newer example. Instead of asking what happened to one famous exercise hormone, researchers could watch hundreds of proteins and metabolites change together. [3]

This shift is changing how scientists think about exercise.

The body may not respond through one magic molecule. It may respond through a moving network of hundreds of signals.

Could Scientists Make an “Exercise Pill”?

This is one of the biggest hopes surrounding exerkine research, but the phrase can be misleading.

Scientists would like to understand whether certain exercise pathways could be used to help people who cannot exercise normally because of severe illness, disability, injury, frailty, or other limitations.

If one exerkine protects nerve cells, improves metabolism, or strengthens a useful immune response, that molecule or its pathway could someday inspire a drug.

The PF4 experiments in aged mice are one example of this idea. [4]

Cancer researchers are exploring a similar idea by studying whether pathways discovered through exercise biology can be activated with medicines. [6]

But exercise affects the heart, lungs, muscles, bones, blood vessels, brain, immune system, metabolism, and many other systems at the same time.

One molecule is unlikely to copy all of that.

The authors of the Nature Reviews Endocrinology review described an “exercise in a pill” as an appealing goal, but one that remains far from reality.[1]

Are Exerkines Proven to Cause the Health Benefits of Exercise?

Some have strong evidence behind them.

For many others, the answer is not yet clear.

Scientists know that exercise changes large numbers of signaling molecules. They also know that regular physical activity can improve health across many organ systems.

Connecting those two facts molecule by molecule is much harder.

Researchers need to show not only that an exerkine changes with exercise, but that the change actually causes an important biological effect.

Human evidence is especially important. A pathway that produces dramatic results in mice may be weaker, different, or absent in people.

Irisin provides a useful example. Early animal studies raised hopes that exercise-linked irisin could help turn white fat into more energy-burning “brown-like” fat. Later human studies produced a much less consistent picture, and whether this pathway has a major role in people remains debated. [1]

That does not make exerkines unimportant.

It means the field is still separating strong biological signals from interesting correlations.

What Makes Exerkines Scientifically Interesting?

Exerkines give researchers a new way to ask an old question: Why is exercise good for so many parts of the body?

For a long time, scientists could describe many of exercise’s results without fully explaining how distant organs coordinated those changes.

Exerkine research offers part of an answer.

Muscle can signal to fat. Fat can signal to muscle. The liver can change circulating factors. Platelets can release molecules that affect the brain. Immune cells can respond to signals produced during physical activity.

The result is not a simple chain with one starting point and one ending point.

It is a network.

That network may help explain why exercise can influence systems that seem far removed from the muscles doing the work.

The Bottom Line

Exerkines are molecular messages linked to exercise.

They can come from muscle, fat, liver, heart, brain, blood cells, and other tissues. They include proteins, hormones, metabolites, fats, and genetic material.

Some travel through the bloodstream. Others act only on nearby cells. Some may even travel inside tiny packages called extracellular vesicles.

Together, these signals help scientists understand exercise as more than movement or calorie burning. Exercise is also a whole-body communication event.

But the science is not finished.

Different workouts can produce very different molecular responses. A signal that rises after one hard session may behave differently after months of training. People can respond differently to the same workout. And many of the most exciting findings about the brain, aging, cancer, and disease still come from animals or laboratory experiments rather than human treatments.

So the most useful way to think about exerkines is not as miracle exercise chemicals.

They are clues to a much larger system.

Every time the body moves, its tissues begin talking to one another. Exerkines are helping scientists learn what those messages say.

References

1. Chow LS, Gerszten RE, Taylor JM, et al. Exerkines in health, resilience and disease. Nature Reviews Endocrinology. 2022;18:273-289. doi:10.1038/s41574-022-00641-2.

2. Novelli G, Calcaterra G, Casciani F, Pecorelli S, Mehta JL. ‘Exerkines’: A Comprehensive Term for the Factors Produced in Response to Exercise. Biomedicines. 2024;12(9):1975. doi:10.3390/biomedicines12091975.

3. Olsen L, Botella J, Barrows D, et al. Exercise intensity modulates interorgan communication and is associated with cardiometabolic health outcomes in humans. Cell Reports Medicine. 2026;102988. doi:10.1016/j.xcrm.2026.102988.

4. Leiter O, et al. Platelets can replicate the benefits of exercise in the brain. Nature Communications. 2023. doi:10.1038/s41467-023-39873-9.

5. Paez-Garcia S, Borda MG, et al. Exercise, exerkines, and muscle-brain crosstalk in Parkinson’s disease. Neuroprotection. 2026. doi:10.1002/nep3.70032.

6. Kurz ES, Bar-Sagi D. Beyond the treadmill: Exercise oncology as a platform for translational advance. EXO – Beyond the Cell. 2026. doi:10.70401/EXO.2026.0015.

7. Doig CL. Understanding Exerkines. The Endocrinologist, Society for Endocrinology. 2022.