Exercise releases myokines from skeletal muscles

Posted on by Jesse Santiano, M.D.

This article was initially published on May 16, 2019. It has been updated.

What is Cytokine?

Cytokines are signaling proteins. Think of cytokines as text messages from one organ to another organ. The signal may be a ‘yes,’ “no,’ ‘make some more” (positive feedback loop), or that’s enough (negative feedback loop).

The signals may be to themselves or the same cell (autocrine), nearby cells (paracrine), and distant organs (endocrine). In a sense, you can say that skeletal muscles are endocrine glands, just like the thyroid, pituitary, and adrenal glands.

What is Myokine?

A myokine is a cytokine or signaling protein from the skeletal muscles. Myo is from muscle, and Kine is from the word cytokine. The skeletal muscles produce hundreds of different kinds of myokines. Research about myokines is just beginning to describe their functions and interactions.

What Organs Are Influenced by Myokines?

Myokines work on fat cells, liver, pancreas, bone marrow, heart, white blood cells, immune cells, brain cells, and even stem cells.

What are the Biological Effects of Myokines?

  1. Metabolic function
  2. Exercise adaptation
  3. Tissue regeneration and repair
  4. Maintenance of healthy bodily functioning
  5. Anti-obesity
  6. Immunomodulation
  7. Cancer prevention
  8. Heat generation
  9. Tissue and blood vessel repair
  10. Possible heart muscle repair to patients with previous heart attacks
  11. Diabetes control
  12. Potential cancer treatment of cancer

No myokine causes disease by itself. Unlike hormones from the thyroid or adrenal, where disease states can happen if produced in excess, like hyperthyroidism or hypercortisolism, there are no diseases known due to excess myokine production.

How do you Produce More Myokines?

Myokine production is stimulated during muscle contraction. The more muscle contract, the more myokines are produced. It does not take many myokines to have an effect. Picomoles are enough. A picomole (pM) is 10­ ¯¹² mol/L.

Myokines and their effects on tissues

Fat cells

  1. Interleukin-6 (IL-6), angiopoietin-like 4 (ANGPTL4) – dissolves fat
  2. IL-15, ANGPTL4 – endothelium decreases lipoprotein lipase activity
  3. Irisin, β-amino isobutyric acid (BAIBA) – turns white fat to brown fat, heat production
  4. Meteorin-like – Heat production
  5. Decreases myostatin– resulting in increased muscle mass lower fat mass. The Belgian blue cow has a mutation that reduces the myostatin function, resulting in significant muscles development.
Belgian blue cow by agriflanders. Wikipedia

Brain

  1. Lowers kynurenine – decreases stress, has beneficial effects on neurodegenerative diseases associated with inflammation.
  2. Cystatin B Protein (CSTB), Irisin produces Brain-derived neurotrophic factor (BDNF) and increases cognitive function.

Pancreas

  1. IL-6 produces beta cells leading to more insulin secretion with higher Glucagon-peptide like- 1 (GLP-1) release
  2. ANGPTL4, IL-6 leads to alpha cell hyperplasia that elevates blood glucose needed during exercise.

Liver

  1. Interleukin- 6 (IL-6) – improves glucose metabolism
  2. Interleukin-10 (L-10) – decreases inflammation

Bone

  1. IGF-1, Secreted protein acidic and rich in cysteine (SPARC), IL-15 – bone formation, increased mineralization
  2. Lower myostatin and promotes bone healing

Gut

IL-6 ⇒ L cells ⇒ increase GLP-1 release for glucose metabolism

Immune cells

  1. IL-10 – an anti-inflammatory cytokine
  2. Interleukin -i receptor agonist (IL-1RA) – IL-1α/ß inflammation
  3. Chemokine (C-C) motif ligand 2 (CCL2) – increase monocyte cell attraction
  4. IL-6 ⇒ macrophages increase alternative activation

Tumor

  1. IL-1, IL-15 – natural killer cell mobilization to remove cancerous cells
  2. SPARC – promotes apoptosis (orderly cell death) to remove old, useless, and precancerous cells.
Picture2
Source: Hoffman and Weigert et al. 

The takeaway message in the image is that exercise produces many benefits to the whole body that no drug can copy.

Interorgan cross-talk is complicated; that is why an “exercise pill” might not be possible. It is better, safer, and much cheaper to EXERCISE to benefit from myokines.

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Reference:

Hoffmann C, Weigert C. Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations. Cold Spring Harb Perspect Med. 2017 Nov 1;7(11).
Photo Credits:
  1. Belgian blue cow By agriflanders – originally posted to Flickr as Kamp- Bambino vd ijzer copy, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=6257487.
  2. Myokines: Christoph Hoffmann, and Cora Weigert Cold Spring Harbor Perspectives in  Medicine 2017;7:a029793  Cold Spring Harbor Laboratory Press