Important: this content is educational and does not replace professional medical advice. If you have a chronic condition, persistent symptoms, take medications, or are pregnant, seek clinical guidance before changing your exercise routine.

Key takeaways

  • Muscle as an endocrine organ: contracting muscle releases myokines that signal to other tissues.
  • Metabolism & fat: some pathways relate to lipolysis and adipose tissue adaptation (e.g., browning/beige features).
  • Brain support: exercise is associated with neurotrophic signaling such as BDNF, linked to plasticity.
  • Consistency matters: effects depend on frequency, progression, nutrition and sleep—no single “magic hormone.”

1. Why myokines matter

For years, exercise was explained mostly through calorie expenditure and muscle strengthening. That view is incomplete when we look at how consistent physical activity is associated with lower risk of diverse outcomes—metabolic disease, cardiovascular risk, cognitive decline and some mood disorders.

One key piece is that skeletal muscle behaves like an endocrine organ. When you move, contracting muscle can release signaling proteins that travel through the bloodstream and influence other tissues. These messengers include myokines.

2. What myokines are

Myokines are signaling proteins released mainly by muscle fibers in response to contraction. They can act locally (within muscle), nearby (paracrine) or systemically (endocrine), influencing organs such as liver, adipose tissue and brain.

The “myokine profile” can shift with exercise type, intensity, duration, training status, and lifestyle factors like sleep and nutrition.

3. Exercise-related IL-6: why context matters

Interleukin-6 (IL-6) is often cited because it can rise substantially during certain exercise protocols. In clinical settings, IL-6 may appear as an inflammatory marker; however, exercise-related IL-6 can have different dynamics and associations—especially because it increases in a context of acute energy demand and muscle contraction.

Characteristic IL-6 in chronic inflammation (example) IL-6 associated with exercise (example)
Context Persistent metabolic stress, illness, visceral adiposity Acute contraction + energy turnover
Time course Long-lasting elevation Transient rise and recovery
Association Higher risk markers (depending on scenario) Metabolic signaling and adaptation pathways

Bottom line: it is rarely accurate to label IL-6 as simply “good” or “bad.” Interpretation depends on the person’s health status, the pattern of elevation, and the broader cytokine environment.

4. Irisin and adipose tissue adaptation

Irisin is frequently discussed as a potential link between exercise and changes in adipose tissue. It is connected to the PGC-1α/FNDC5 axis and, in experimental models, has been linked to increased thermogenic features in fat tissue (often described as “browning” or “beige” adaptation).

For practical health education, the key point is: there is no single exercise hormone that guarantees weight loss. Real-world outcomes depend on sustained training, energy balance, diet quality and recovery.

Practical note

If your goal is body composition, focus on what consistently drives results: progressive resistance training + aerobic activity + adequate protein + sufficient sleep. Myokines may be part of the mechanism, but habits drive outcomes.

5. Muscle–brain axis and BDNF

Exercise does not only change muscle. It can also influence brain-related signaling. One widely discussed marker is BDNF (Brain-Derived Neurotrophic Factor), involved in neuronal plasticity and hippocampal health.

“Exercise shifts the biochemical environment that supports the brain.”

Many studies report acute BDNF increases with certain protocols and, over time, associations with improved mood and cognition. Individual responses vary with age, baseline fitness, stress and clinical conditions.

6. Other myokines and key pathways

Beyond IL-6 and irisin, the literature discusses several other signals and pathways. Here is a simplified map:

Because the exercise “signal cocktail” is broad, it is usually misleading to reduce the story to a single molecule.

7. How to optimize in practice

There is no one-size-fits-all “best” workout for myokines. For general health, combining complementary stimuli and progressing safely is usually the best approach:

  1. Aerobic base: ~150–300 min/week moderate intensity (or 75–150 vigorous), adjusted to your level.
  2. Resistance training 2–4×/week: prioritize technique, progressive overload and consistency.
  3. Intervals (optional): 1–2×/week once you have a base and adequate recovery.
  4. Recovery: sleep and lighter days; chronic overload increases injury risk and reduces adherence.

If you are starting, adherence beats micro-optimization. Build the habit first.

8. Exercise as a “polypill”

The “exercise as medicine” idea is compelling because training influences multiple systems at once: cardiometabolic health, musculoskeletal function and brain-related pathways. Rather than targeting one pathway, physical activity triggers multiple adaptations—and myokines are one plausible part of this systemic communication.

The most useful takeaway is practical: treat training as a health habit with realistic goals and progressive consistency.

Frequently asked questions

What are myokines?

Myokines are signaling proteins released mainly by skeletal muscle during contraction. They can influence metabolism and communication with organs such as liver, adipose tissue and brain.

Is there a single “exercise hormone” that causes weight loss?

No. Molecules like irisin may participate in adipose tissue adaptation, but weight loss is driven by consistent training, energy balance, nutrition and recovery.

Is IL-6 always inflammatory?

IL-6 appears in different contexts. Chronic elevation can be associated with risk markers, while exercise-related IL-6 can rise transiently and correlate with metabolic signaling. Context matters.

Which workouts stimulate myokines the most?

Different training styles trigger different pathways. Aerobic volume and resistance/interval intensity can complement each other. A balanced plan with safe progression is usually best.

Does exercise support brain health?

Many studies associate regular exercise with improvements in mood and cognition and with changes in neurotrophic signaling (including BDNF). Individual responses vary and clinical care may still be necessary.

Selected references

[1] Pedersen BK. Physical activity as medicine: myokines as mediators. Current Opinion in Physiology (2019).
[2] Bostr\u00f6m P, et al. A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat. Nature (2012).
[3] Wrann CD, et al. Exercise induces hippocampal BDNF through a PGC-1\u03b1/FNDC5 pathway. Cell Metabolism (2013).
[4] Reviews on myokines and endocrine functions of skeletal muscle (see PubMed for updated syntheses).