Since the very first muscle derived myostatin protein was identified as a myokine in 1997, over 600 myokines have been identified to date (Gorgens et al., 2015).  However, the majority of these myokines are still not sufficiently characterized.

Why is this important? This frequently neglected topic plays a central roll in diet and exercise in those people trying to lose or maintain their weight. Myokines are the key actors in muscle development and size, and and they influence weight gain or loss in a pretty dramatic way.

The myokines are a subclass of interlukins. Interlukins are a group of naturally occurring proteins that mediate communication between cells. They are like the rapid text messages between teenagers in the same room communicating with each other. Interleukins regulate cell growth, differentiation, and motility. They are particularly important in stimulating immune responses, such as inflammation.

Muscles Make Their Own Interlukins

A few years ago, research demonstrated in the Journal of Experimental Biology that there is a notable increase in the plasma concentration of IL-6 during exercise (Pedersen and Febbraio, 2008). This is followed by the appearance of IL-1 receptor antagonist (IL-1ra) and the anti-inflammatory cytokine IL-10. Concentrations of the these cytokines, IL-8, macrophage inflammatory protein 1a (MIP-1a) and MIP-1b are elevated after strenuous exercise.

Thus, the cytokine response to exercise is not preceded by an increase in plasma TNF-a. Even though there may be a moderate increase in the systemic concentration of these cytokines, the underlying fact is that the appearance of IL-6 in the circulation is by far the most marked and precedes that of the other cytokines (Pedersen and Febbraio, 2008).

Muscle Interlukins Create Good Inflammation

When IL-6 is produced by macrophages, it leads to an inflammatory response, whereas muscle cells produce and release IL-6 without activating classical pro-inflammatory pathways. The fact that IL-6 can sometimes act as a pro-inflammatory and sometimes as an anti-inflammatory agent appears to be more dependent on the environment (muscle versus immune cell) than on whether IL-6 is activated in an acute or chronic fashion (Pedersen and Febbraio, 2008). This essentially means that strenuous exercise is a good form of stress, stabilizing the muscle, causing growth and not adversely affecting the immune system.

Interlukins From Muscles Talk to Fat Cells

At the same time, IL-15 is expressed in human skeletal muscle (Pedersen et al., 2007). C2C12 tubule contraction in the muscle stimulates the IL-15 release. It possesses anabolic effects on skeletal muscle in vitro and in vivo and may also take part in reducing adipose tissue mass (Pedersen et al., 2007). Therefore, IL-15 has been suggested to be involved in muscle–fat crosstalk. Recently, we demonstrated that IL-15 mRNA levels were upregulated in human skeletal muscle following a bout of strength training (Nielsen et al., 2007), suggesting that IL-15 may accumulate within the muscle as a consequence of regular training.

What is fascinating is that there is a negative relationship between IL-15 and truncal fat mass, but not limb fat mass. That means that the more resistance exercise you participate in regularly, the lower your truncal fat becomes.

BDNF Stays Active Even After Exercise

Another cytokine actor in this opera of human metabolism is Brain Derived Neurotrophic Factor (BDNF). BDNF is a fascinating hormone produced in the brain. In humans, a BDNF release from the brain was observed at rest and increased 2- to 3-fold during exercise. Both at rest and during exercise, the brain contributed 70–80% of the circulating BDNF, while this contribution decreased following 1h of recovery. In mice, exercise induced a 3- to 5-fold increase in BDNF mRNA expression in the hippocampus and cortex, peaking 2h after the termination of exercise.

Matthews and colleagues studied whether skeletal muscle would produce BDNF in response to exercise (Matthews et al., 2009) and found that BDNF mRNA and protein expression were increased in human skeletal muscle after exercise. However. muscle-derived BDNF appeared not to be released into the circulation. BDNF mRNA and protein expression were increased in muscle cells that were electrically stimulated.

You can augment the presence of BDNF with curcumin.  Curcumin is a natural isolate derived from turmeric an has been show to have anti-inflammatory, anti-oxidant and anti-depressant properties through its ability to raise BDNF.  Using curcumin daily with a regular exercise program helps to improve brain function and reduce mental and physical stress (4, 5)

How HIFEM Exercise Is Effective

Why is this important? Because, BDNF increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and enhanced fat oxidation both in vitro and ex vivo. In layman’s terms, that means that regular exercise stimulates the burning of fat for 1-2 hours after exercise. This can be exercise from resistance training or from HIFEM like EMSculpt or electromagnetic stimulus.

What is the take home message from all this geeky science stuff?

Resistance exercise improves muscle regeneration, fatty acid oxidation, fat metabolism, muscle repair, mitochondrial biogenesis (increasing numbers of mitochondria). So if you are not participating in at least 3 days of resistance exercise per week, I’d encourage you to do so.

If you are looking for a simple body weight exercise program that can be done at home. I’ll send you my program for free. Go to docmuscles.com/exercise and sign up.

References:

1. Pedersen BK. Muscles and their myokines. J Exper Biol. 2011. 214:337-346. doi:10.1242/jeb.048074.
2. Furuichi Y, Manabe Y, Takagi M, Aoki M, Fujii NL (2018) Evidence for acute contraction induced myokine secretion by C2C12 myotubes. PLoS ONE 13(10): e0206146. https://doi.org/ 10.1371/journal.pone.0206146.
3. Han LJ & Hee-Sook J. Role of Myokines in Regulating Skeletal Muscle Mass and Function. Frontiers in Physiology. Jan 2019. Vol 10:1-9. doi: 10.3389/fphys.2019.00042
4. Ga-Young Choi, Hyun-Bum Kim, Eun-Sang Hwang, Seok Lee, Min-Ji Kim, Ji-Young Choi, Sung-Ok Lee, Sang-Seong Kim, Ji-Ho Park, “Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats”, Mediators of Inflammation, vol. 2017, Article ID 6280925, 9 pages, 2017. https://doi.org/10.1155/2017/6280925
5. Hurley LL, Akinfiresoye L, Nwulia E, Kamiya A, Kulkarni AA, Tizabi Y. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF, Behavioral Brain Research. 2013(239):27-30. ISSN 0166-4328, https://doi.org/10.1016/j.bbr.2012.10.049.