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Myokines and Weight Loss
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:
- Pedersen BK. Muscles and their myokines. J Exper Biol. 2011. 214:337-346. doi:10.1242/jeb.048074.
- 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.
- 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
- 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
- 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.
Why Add EMSculpt and EMSella to My Practice?
I just added two amazing treatments to our office toolbox: EMSculpt and EMSella. I am so excited about these two treatments.
Why add these to the practice? As a family practitioner who focuses on the treatment of insulin resistance, pre-diabetes, diabetes and obesity, I’ve been looking for safe and effective ways to improve muscle and decrease fat. Ketogenic and carnivorous diets are the most effective way to do this naturally, of course including a good exercise program should be a significant part of these diets. Yet, many of my patients over 40 are already seeing the effects of aging, obesity and muscle decline.
Lack of core strength leads to gait instability, weakness, increased likelihood of falling and breaking a hip. Poor core strength is also a factor in incontinence, erectile dysfunction and poor sexual function.
We know that improving core strength has a very powerful positive effect in reducing these problems. Yet, a significant number of my patients over 65 have a hard time exercising due to arthritis and other diseases.
These are revolutionary devices that simultaneously emit both radiofrequency and high-intensity electromagnetic energies (HIFEM).
The end result is more fat reduction and muscle growth than any single gold-standard product for less time and less money. . . 25% more muscle and 30% reduction in fat on average after just four treatments*.
When used with a ketogenic or carnivorous diet, these treatments are a game changer for getting rid of that last bit of stubborn fat.
In combing EMSculpt for the abdomen and EMSella for the pelvic floor, it creates “core to floor” muscle strengthening and stability that is an amazing and very effective adjunctive treatment to a regular exercise program.
These treatments are perfect for postpartum mothers, men, elite athletes and women who suffer from incontinence. They are all a perfect fit for this treatment as results include improved strength, balance and posture; alleviated back pain; and improved urinary issues and sexual health in both men and women. When EMSella is used in conjunction with other muscle development devices like Emsculpt, you’re building core strength, posture developments and sexual health improvements for both men and women.
And, although core strength is not something you see, it is something you can definitely feel.
Call our office for your first treatment today!!
*US FDA clearances:
Your results may vary. You may feel intense heat during the treatment, but it should never be painful. If you experience pain during the treatment, immediately discontinue the treatment and speak with your treatment provider. Treatment should not be applied over scar tissue, or if you have electronic or metal implants. As with any heat-based therapy, burns may result. As with any medical procedure, ask your doctor if the EMSCULPT NEO® procedure is right for you. EMSCULPT NEO® is indicated for non-invasive lipolysis (breakdown of fat) of the abdomen and thighs and reduction in circumference of the abdomen and thighs with Skin Type I to Skin Type VI; and for non-invasive lipolysis (breakdown of fat) of the upper arms limited to skin types II and III and BMI 30 or under. EMSCULPT NEO® is also indicated for improvement of abdominal tone, strengthening of the abdominal muscles, development of firmer abdomen; strengthening, toning, and firming of buttocks, thighs, and calves; and improvement of muscle tone and firmness, for strengthening muscles in arms.
High Fat? High Protein? Low Protein? What is really ketogenic?
The daily question that I get asked by my patients, and from those around the internet, relates to burning one’s own fat. “Don’t you have to limit the calories and limit fat you eat to burn your own body fat?”
It seems everyone has a differing opinion on this question and a few of them have two opinions (you know who you are). Very few of these opinions are grounded in the actual science of weight loss.
I hear coaches, trainers and even a number physicians argue, name call and rant about the need to cut calories to lose fat. Yet, most of my patients “cut their calories” 200-1000 per day without successful fat reduction. They may increase their exercise by 400-600 calories per day and still no weight loss. This is the same crazy ineffective instruction we’ve been given for the last 50 years.
To be honest, there is a percentage of those in the fitness and modeling worlds upon which this dogma is effective and that is because of normal insulin levels and significant exercise. However, for the other 85% of the world who work over 40-80 hours a week, have children and families, serve in our churches and occasionally have a social life, myself included, it doesn’t work. If we were all paid to exercise 2 hours a day and take “butt selfies” on Instagram, it might be easier.
Yes, you will probably lose 20 lbs. with calorie restriction, but your testosterone will drop by up to 50%, sex hormone binding globulin will double, and over time your basal metabolic rate will slow due to dramatic and often permeant reduction in thyroid function. This makes it nearly impossible to lose more than that 20 lbs, and then you will regain the weight once calorie levels return to normal within 18-24 months. (No one ever talks about that little problem, do they?)
For those of you that want to see success in weight loss, let’s outline a few essential principles that the trainers, keto-coaches and social media talking heads aren’t mentioning.
First, insulin has to be kept at a baseline. The reason that 85% of people don’t, won’t and can’t see effective weight loss beyond 20-30 lbs long term (greater than 2 years) with calorie restriction is that 85% of the population has some degree of insulin resistance. It’s not a disease, it’s a syndrome associated with the effect of the standard American diet. I wrote a whole book about it called The Keto Cure. We know that insulin and catecholamines increase the rate by which fat is stored.
Second, glucacon is a counter active hormone to keep your blood sugar from bottoming out. The presence of glucagon stimulates fat burning. Intermittent fasting and ketogenic dietary intake allow blood sugar to drop below 70 mg/dL (3.9 mmol/L) causing glucagon release and stimulate increased release of free fatty acids from the fat cells.
Third, two hormones, epinephrine and norepinephrine, are produced when blood sugar drops below 67 mg/dL (3.7 mmol/L). Exercise lowers blood sugar to this level and stimulates additional burning of fat by engaging the release of glucagon and epinephrine and norepinephrine. Exercise, also, has three other myokine hormonal effects making weight loss more successful when the diet is correctly balanced.
The fourth principle that is essential to understand relates to growth hormone. Growth hormone stimulates and preserves muscle tissue, has a suppressive effect on insulin. Growth hormone increases with exercise, sleep, intermittent fasting and when protein intake is at least greater than 90 grams per day in women and around 1 gram of protein per body weight in men. This is notably higher than previous calculations on protein that I have written about in the past. Recent research, also found here, here and here, demonstrates that increased protein above 90-100 grams per day enhances muscle growth and stabilization and further suppresses insulin production beyond what we previously understood.
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Contrary to what the media has been saying about protein sources, not all protein is absorbed in the same way. When it comes to absorption in the human gut and use by the human metabolism, protein sources differ in their effectiveness:
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- Egg protein utilization – 50%
- Meat protein utilization – 40%
- Cheese protein utilization 35-40%
- Whey protein utilization – 18%
- Vegetable protein utilization – 14%
Lastly, release of fat from the fat cell is mediated by natriuretic peptides and cGMP through the release of catecholamines, prostaglandins and nicotinic acid. Interestingly, the major positive regulators of human lipolysis are catecholamines and natriuretic peptides (NPs). Fatty acid release from fat cells triples when catecholamines and natriuretic peptides are released. Catecholamines are produced by exercise, stimulants and stress, and natriuretic peptides are stimulated by short change fatty acids (ketones).
For the science geeks in who follow my blog, I’ve included the following picture that summarizes the effects of these hormones on the fat cell. The figure below shows the major pathways by which insulin, thyroid, catecholamines, testosterone and sympathomimetics effect fatty acid release from adipose tissue.
The take home message from this information is this, effective long term weight loss cannot be achieved by calorie restriction. Effective weight loss (specifically fat loss and muscle gain) is most effectively achieved when carbohydrates are restricted, protein is optimized, and proper exercise adequately triggers the release of fat burning hormones.
Click HERE and get a copy of my ketogenic diet.
Get a copy of my diet and 13 learning modules with coaching and online assistance by becoming a member of Dr. Nally’s KetoClan.
I’d like to know, what combination has been most effective for you?
Have a great day!
Adam (eat your bacon) Nally, DO