I did my Legs/Abs rotation at Fike this past Tuesday. It was a good workout overall, except for the “goblet squats” that I had to resort to when all the squat racks and leg presses were occupied. Through co-contraction and lingering in the lower turnaround, I got the desired effect, but the whole process felt like a monument to outroading.
Hammer Clam Shell Abdominal
I know you all are probably tired of hearing me go on about myokines, but I really do believe that they will offer us insight into a lot of what we argue and speculate about. More importantly, they will uncover objective health and disease-prevention benefits that may change the practice of medicine. Perhaps one day we will see commercials that say…”ask your doctor if diet and exercise are right for you”. One of the ways that I know that this may represent a big breakthrough for exercise, is the fact that the literature is not coming out of the exercise physiology community, but is instead coming from departments of cell biology, biochemistry and physiology. With that in mind I offer the following review article from the Journal of Applied Physiology entitled: Edward F. Adolph Distinguished Lecture: Muscle as an Endocrine Organ: IL-6 and other myokines. I am providing a link to the full text article here: http://www.jappl.org/content/107/4/1006.full. I highly suggest taking some time to review the entire article, as it will begin to tie together for you how muscle has effects on other tissues that seem out of proportion to their simple contribution to energy balance. I will give you a brief rundown of the effects of the major myokines below.
IL-6- This myokine is liberated from contracting skeletal muscle and is currently the most well-understood myokine. Its concentration increases 100-fold shortly after a bout of contraction. This abrupt increase entrains an increase in IL-6 receptor (IL-6R) sensitivity. The increased IL-6R sensitivity results in a lower basal level of IL-6 when exercise is not occurring. This seems to be a mechanism whereby exercise tolerance and recovery are mediated. The rapid rise of IL-6 during exercise seems to occur as a result of an amplification cascade and it precedes the release of inflammatory cytokines that are released during exercise. IL-6 also seems to be an energy sensor, as it tends to amplify more during low-glycogen states and its release can be inhibited by glucose ingestion during an exercise bout. Release of Nitric Oxide (NO) in contracting skeletal muscle seems to be a pre-translational signaling event that is required for the enhanced release of IL-6, so a pump does seem to feel good for a reason. IL-6 also underpins the amazing metabolic adaptability of skeletal muscle. IL-6 helps to augment to adaptions both in glucose and fatty acid oxidation in response to substrate availability. Fatty acid oxidation is increased and glucose uptake and utilization are optimized. IL-6 can also function as a Leptin surrogate to activate insulin signaling, which in turn improves insulin sensitivity, explaining why IL-6 knockout mice develop obesity and diabetes. IL-6 receptor sensitivity correlates directly with exercise tolerance and is in fact trainable, suggesting that recovery ability may be more trainable than we previously thought. I seriously wonder if fibromyalgia and chronic fatigue will be found to be linked to problems with IL-6 production or receptor sensitivity. IL-6 is also a powerful anti-inflammatory agent, but it is a pro-inflammatory agent. In other words, as IL-6R sensitivity decreases and IL-6 levels rise, more inflammation will occur. This lack of IL-6R sensitivity is thought to be the underlying reason for the systemic inflammation and loss of insulin receptor sensitivity in the metabolic syndrome.
IL-15- This myokine got some coverage in Chapter 8 of BBS for its role in determining one’s potential muscle mass. Its major role however, is in muscle-fat cross-talk. IL-15 mRNA levels (genetic signal to be like Doritos and make more) is upregulated in human skeletal muscle after a single bout of strength training suggesting that IL-15 may accumulate in muscle as a consequence of regular training. One of the major effects of IL-15 is the reduction in fat mass, particularly trunkal/abdominal fat (which is the fat that produces the most inflammatory cytokines known as adipokines). IL-15 may be involved in signaling that signals “uncoupling protein” which converts energy-storing white fat into heat-liberating brown fat. IL-15 has also been shown to increase bone mineral content. The changes in fat mass are irrespective of the energy balance contribution of the activity, and the effects of bone mineral content are irrespective of mechanical loading issues as these effects are seen with simple infusion of IL-15 in lab animals. The exact signaling pathways for these effects are not yet known, but are a fertile ground for ongoing scholarly activity.
IL-8- IL-8 was previously known as a chemokine that attracted neutrophils (white blood cells) during infection or tissue damage and was also known to be involved with angiogenesis, tumorogenesis and metastasis of cancer cells. However, these were its systemic effect. Recent findings have shown that IL-8 has a local effect within skeletal muscle that are triggered by exhaustive exercise. The major effect is to signal angiogenesis (the development of new blood vessels) to serve the working muscle and provide the supply network to service new muscle growth. IL-8 has some systemic effects that are worrisome, but fortunately, IL-8 produced in skeletal muscles exerts only local effects and is not released into the systemic circulation.
BDNF- BDNF is a member of the neurotrophic family of cytokines that promotes the survival, growth and maintenance of neurons. BDNF thus plays a major role in learning and memory. Like many things in life, BDNF’s value is most when we lose it. BDNF has been shown to be decreased in Alzheimer’s disease, major depression, memory impairment unrelated to dementia, obesity, type II diabetes and is an independent marker for mortality in the elderly. BDNF also increases fat oxidation. BDNF has been shown to be increased in skeletal muscle as a result of exercise, but has not been shown to be released into the circulation. However, BDNF work in both an autocrine and paracrine fashion and its effects may be related to total body stores and not circulating levels.
Myomouse and other Cytokins- Kenneth Walsh in Boston has created a very muscular mouse called “myomouse” by manipulating a gene for “myogenic Akt” signaling. The resultant animal demonstrates increased muscle mass, decreased fat mass and optimized whole body metabolism. Walsh has devised a protocol to discover new myokines that confer the phenotypic changes brought on by myogenic Akt induction. As a result he has recently discovered FGF21 (previously known to be induced by fasting) which causes increased fatty acid utilization as well as increased gluconeogenesis (making glucose from end products of glucose metabolism or proteins) with out increasing glycogenolysis (glycogen breakdown)…in other words you can make new glucose without having to tap your glucose stores (not eating your metabolic seed corn). This animal model promises to uncover many new myokines in the future.
Just some of the descriptors of these myokines triggers some questions in my head. For instance, can IL-6R sensitivity be optimized on a certain continuum of intensity/volume/frequency? Could this be why some experience ROBAT more aggressively when they go to infrequent consolidated routines. Is there some defect in IL-6R sensitivity that underlies fibromyalgia that could be corrected with proper exercise dosing? Does IL-6R sensitivity correlate with my notion of “the active genotype” and the rise in NEAT (non-exercise activity therom0genesis) in my clients? If IL-8 is released during exhaustive exercise, could super high intensity techniques result in levels that allow leakage into the general circulation causing unintended systemic inflammation, and could this be the biomarker for “outroading” or ROBAT? (run over by a truck, for those unfamiliar with the lingo). Could subfailure sessions have some value by the action on keepin IL-6R sensitivity high between higher intensity sessions? Could the myomouse demonstrate the optimal balance of myokines that correlates with this particular phenotype? If so, could we collect data on how protocol affects these ratios and finally come up with a way to replicate the myokine profile of the myomouse as a means of optimizing our own body composition and metabolism? All I can offer at this point is to quote Glenn Reynolds at Instapundit and say….”FASTER PLEASE”.
Post your WOW’s and your thoughts.