My most recent workout was done on a mini-vacation to Myrtle Beach.  I was due for Chest/Back so I did the Following:

Dumbbell Row, Dumbbell Flat Bech Press, Pulldown (technogym with motion similar to old Nautilus Rotary Latissimus machine), Dumbbell Incline Press, Dumbbell Deadlift.  This was a great workout.  Left me quite sore, but not systemically drained.

Today Wendy did her workout at UE:  MedX Chest Press, SS Systems Pulldown, MedX Overhead Press, MedX Leg Press, TSC hip adduction/abduction, TSC neck flexion/extension.

BBS follower Ricardo sent the following NY Times article on myokines and how they keep your skin looking young.  While not specific to strength training, the article is specific to IL-15 which has been shown to be released with strength exercise.  The link to the article is below for your perusal.

http://well.blogs.nytimes.com/2014/04/16/younger-skin-through-exercise/?_php=true&_type=blogs&_r=0

Post your WOW’s and your thoughts.

I did the following workouts over the past week.  I did legs/abs at Fike Gym and Back/Chest/Neck at UE.

3/31 at Fike:  Calf Press, Leg Extension (full extension from 3rd rep on), Leg Curl, Hammer Leg Press, Hammer Clam Shell Abdominal

4/06 at UE:  SS Systems Pulldown, MedX Chest Press (horizontal handles), SS Systems Neck Flexion, Nautilus Pullover with SS retrofits, MedX Chest Press (vertical handles), MedX Row with SS cam, SS Systems Neck Extension.

Both workouts were great.  I recovered well despite a very hectic week in the ER.

There has been much debate in the past about whether resistance training significantly affects hormonal profiles as it pertains to muscle growth.  There is little evidence to show that increases in sex steroids or growth hormone are contributing factors to the growth mechanism.  However, recent research does indicate that resistance training does improve overall hormonal profiles as the relate to general health and sexual function.  This recent study shows that resistance training can restore the activity of enzymes involved in sex steroid synthesis, and ultimately testosterone levels in older male subjects.  Activity levels were restored to youthful levels in this study.

The problem with T supplementation or drugs for erectile dysfunction is that the thought process is like pushing with a rope.  Rather than trying to create the right conditions for the end product, you just supply the end product.  The problem is that the end product is part of a feedback loop; when you supply it exogenously, you further inhibit production.  With resistance exercise you are create the proper stimulus to require the desired end-product, thus keeping both sides of the feedback loop stimulated and balanced.  You get the end product as a result of stimulated production rather than as a supplied entity that shuts down production.

FASEB J. 2014 Apr;28(4):1891-7. doi: 10.1096/fj.13-245480. Epub 2014 Jan 17.

Resistance training restores muscle sex steroid hormone steroidogenesis in older men.

Abstract

Skeletal muscle can synthesize testosterone and 5α-dihydrotestosterone (DHT) from dehydroepiandrosterone (DHEA) via steroidogenic enzymes in vitro, but hormone levels and steroidogenic enzyme expression decline with aging. Resistance exercise has been shown to increase in plasma sex steroid hormone levels. However, it remains unclear whether resistance training can restore impaired steroidogenic enzyme expressions in older individuals. Six young and 13 older men were recruited, and muscle biopsies were taken from the vastus lateralis at basal state. The same group of older subjects underwent resistance training involving knee extension and flexion exercises for 12 wk, and post-training biopsies were performed 4-5 d after the last exercise session. Muscular sex steroid hormone levels and sex steroidgenesis-related enzyme expressions were significantly lower in older subjects than younger ones at baseline, but 12 wk of resistance training significantly restored hormone levels (DHEA: 432±26 at baseline, 682±31 pg/μg protein, DHT: 6.2±0.9 at baseline, 9.8±1.4 pg/μg protein). Furthermore, the steroidogenesis-related enzymes such as 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, and 5α-reductase expressions were significantly restored by resistance training. We conclude progressive resistance training restores age-related declines in sex steroidogenic enzyme and muscle sex steroid hormone levels in older men.-Sato, K., Iemitsu, M., Matsutani, K., Kurihara, T., Hamaoka, T., Fujita, S. Resistance training restores muscle sex steroid hormone steroidogenesis in older men.

Ask your doctor if diet and exercise are right for you!

Post your WOW’s and your thoughts

The goal is to drive the nail all the way in, flush with the board.  This is the desired level of inroad, fatigue, weight exposure and metabolic work…the “pop-up timer”.

Nail Gun:  This can drive the nail to the desired location with a single action.  As a result, you can accomplish a lot in a shorter span of time.  This is analogous to proper use of RenEx equipment, SuperSlow Systems equipment (in good condition), Retrofitted MedX and Nautilus (in good condition) and certain select pieces from other manufactures such as Cybex or Nautilus.  Properly done, one set gives you all that you need or can stand.  You can stimulate the entire body in short order.  There is little wasted work energy dissipated in the process.  BTW, timed static contraction probably falls in the category, many times requiring no equipment.

Hammer:  This is an elegant and effective tool for getting the job done.  You can drive the nail in with one strike (remember the Karate Kid?), but you also run a risk of bending the nail and subverting the end goal.  Unless you are very practiced, it is likely a better approach to take a more modulated run-up to the end goal, using more controlled and focused strikes until the head of the nail is quite close to the board and then you can finish it off with some hard strikes.  Most barbell movements fit the hammer analogy.  You could squat single set to failure and get a great HIT/BBS effect, but you also will dissipate some energy (ding the board) and are much more likely to bend the nail (lose form and tweak your back, for instance).  Instead I find these movements can still achieve the goal efficiently but through use of cluster sets or jreps.  In cluster reps instead of reaching failure in 12 continuous reps, you might set a goal of performing 5 very solid reps and then resting an interval (anything between 10 and 30 seconds) then repeat 5 reps focusing on perfect form and hard contractions, then rest and keep repeating 5 reps until you get to a cluster where you fail before completing 5 reps.  This basically gives you a running start at any complicating sticking points so that you accumulate adequate contraction and fatigue rather than premature failure due to not being able to overcome the sticking point.  Jreps would involve dividing the movement above and below the sticking point(s), using a weight where you can show perfect form and then working in the hardest zone, then the easier zone(s).  If there are safety issues, the hard zone can be worked close to failure and only the easy zones taken to failure.  John’s Max Pyramid is another variation of making multiple strikes with the hammer to reach the end goal.  With MP you select a very light weight to hold statically at the point of minimum leverage (mid range for most compound movements) for 20 seconds.  Then you jump the weight and repeat.  Do the increases until you cannot make the 20 second mark.  Then go back down the pyramid in the same fashion.  Your set is done when you reach a weight where you can hold for the full 20 seconds or you arrive at your ridiculously light starting weight.  The “hammer” approach applies to most barbell movements and machines that have strength curve issues, but still have acceptable levels of friction.

Rock: This is a really poor tool for the job.  You will have to be very cautious and measured to get the job done.  Even so, you will likely damage the hand holding the nail, have chunks of the tool fly off and when you finally get down to the board, you will likely ding the board as well.  If you are in a survival situation you may elect to use this tool, but most times you will just wait.  Examples include certain barbell movements done incongruently (see the writings and videos of Bill De Simone-enter Moment Arm Exercise at Youtube or your search engine) for examples of what to do and what not to do.  The most common examples however are poorly designed machines.  Unfortunately, this includes most modern manufactured equipment.  Poor biomechanics married with high friction and poor strength curves results in a “rock” that is not worth using.  These really require workarounds and many times will still leave you frustrated.  Think of almost every hotel gym you have been at.  Think of Curves.  Think of the health clubs or university gyms that replaced an entire line of MedX with the latest line of popular equipment.

My latest WOW’s

3/23: Lumbar Extension on SS Systems Pulldown, MedX Chest Press (horizontal handles), Nautilus Pullover with SS retrofits, MedX Chest Press (vertical handles with hand adduction throughout-squeeze handles together), MedX Compound Row with SS cam, SS Systems neck flexion/extension.  All done at UE-Nail Gun style

3/28:  Barbell Overhead Press (cluster 5’s), Dumbbell rear delt (jrep halves), Dumbbell lateral raise (jrep halves), EZ barbell curl (MAE), EZ lying triceps extension (MAE), EZ reverse curl (SSTF), Dumbbell Shrug, MAE forearms using same dumbbells from shrug.  This workout was representative of the “Hammer” approach.

Post your WOW’s and your thoughts.

Here is an update of my last 2 WOW’s.  Chest and Back was done at Fike Gym, and Shoulders/Arms was done at UE.  I kind of wore myself out on the myokine post, and I simply cannot find any studies or topics to post with my most recent WOW’s.  We will therefore leave the responses open to general discussion.

Chest/Back at Fike:  Hands supinated Chins, Dumbbell Bench Press, Dumbbell Rows, Dumbbell Incline Press, Hammer Pulldown, Chest Fly

Shoulders/Arms at UE:  MedX Overhead Press, Bent Fly (rear delt)-Jrep halves, Thick Bar Curls, Nautilus Plate Load Triceps, Thick Bar Wrist Flexion/Extension

Post your WOW’s and your thoughts

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.

Calf Exercise

Leg Extesnion

Leg Curl

Goblet Squat

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.

I am still doing my 3 way split routine.  My two most recent workouts were both done at UE.  Wendy also did her every 14th day workout.

Back/Chest/Neck:  SuperSlow Systems Pulldown, MedX Chest Press(horizontal grip), MedX Compound Row with SS cam, SuperSlow Systems Neck Extension, MedX Chest Press (vertical grip), SuperSlow Systems Neck Flexion, Nautilus Pullover with SS retrofits

Shoulders/Arms:  MedX Overhead Press, Infimetric Rear Delt, EZ Barbell Curl, Triceps Press on SS Systems Pulldown, Formulator Flex/Ext

Wendy:  MedX Chest Press, SuperSlow Systems Pulldown, MedX Overhead Press, TSC Hip Adduction/Abduction as pre-exhaust for MedX Leg Press, TSC Neck Flexion/Extension

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Above are some photos from these sessions.

One of the most common questions I get from people new to BBS is if training so intensely raises blood pressure, or if it is safe for those with hypertension.  We cite numerous studies in BBS that shows that blood pressure and systemic vascular resistance actually decrease during high intensity strength exercise and that it lowers blood pressure over the long term.  This week I wanted to post a recent article that demonstrates that high intensity strength exercise also lowers blood pressure in the short term.  Even more interesting is that the decrease registered the morning after a training session was actually lower in the group that trained to muscular failure when compared to those who did not train to failure.  Once again, it seems there is almost nothing that high intensity strength exercise cannot benefit.

BMC Cardiovasc Disord. 2013 Nov 19;13:105. doi: 10.1186/1471-2261-13-105.

Resistance exercise leading to failure versus not to failure: effects on cardiovascular control.

Abstract

BACKGROUND:

The aim of the present study was to evaluate the acute effects of resistance exercise (RE) leading to failure and RE that was not tofailure on 24 h blood pressure (BP) and heart rate variability (HRV) in sedentary normotensive adult women.

METHODS:

Ten women (33.2 ± 5.8 years; 159.3 ± 9.4 cm; 58.0 ±6.4 kg; body fat 28.4 ± 2.8%) randomly underwent three experimental sessions: control (40 minutes of seated rest), RE leading to failure with 3 sets of 10 repetitions maximum (10-RM), and RE not to failure at 60% of 10-RM with 3 sets of 10 repetitions. Immediately post session BP and HRV were measured for 24 h.

RESULTS:

Ratings of perceived exertion and heart rate were higher during the 10-RM session when compared with 60% of 10-RM (6.4 ± 0.5 vs 3.5 ± 0.8 and 123.7 ± 13.9 vs 104.5 ± 7.3 bpm, respectively). The systolic, diastolic and mean BP decreased at 07:00 a.m. after the 10-RM session when compared with the control session (-9.0 ± 7.8 mmHg, -16.0 ± 12.9 mmHg and -14.3 ± 11.2 mmHg, respectively). The root mean square of the squared differences between R-R intervals decreased after both the 60% of 10-RM and 10-RM sessions compared with the control session.

CONCLUSIONS:

An acute RE session leading to failure induced a higher drop of BP upon awakening, while both RE sessions reduced cardiac parasympathetic modulation. RE may be an interesting training strategy to acutely decrease BP in adult women.

PMID:
24252583
[PubMed - in process]
PMCID:
PMC3840620
Post your WOW’s and your thoughts.

I have gone through the full cycle of my 3 way split since my last posting.  Here is what I did.

Shoulders/Arms:  MedX Overhead Press, Rear Delt Fly, Lateral Raise, Nautilus Plate Load Biceps, Nautilus Plate Load Triceps, EZ reverse Curl, Wrist Flexion (all done at UE)

Legs/Abs:  Calf Exercise, Leg Extension, Leg Curl, Leg Press, Hammer Clam Shell Abdominal (done at Fike Gym)

Back/Chest:  MedX Compound Row, SuperSlow Systems Neck Extension, MedX Chest Press (horizontal handles), Nautilus Pullover, MedX Chest Press (vertical handles while applying adduction force), SuperSlow Systems Neck Flexion, SS Systems Pulldown

Over the years we have had some fairly dramatic functional improvements with our clients at UE.  I had a colleague with severe COPD that came to the ER in respiratory failure who I had to talk into going on the ventilator (he initially refused, stating he wished to die).  After a month on the ventilator he was discharged.  I promised him that if he survived he could come be a UE client and that I would try to make him stronger.  He survived almost another decade, during which time he doubled his strength, lost his oxygen requirement and went on several cruises and vacations with his wife.  We have had several clients discard their walkers and canes.  We have provided pre and post chemotherapy conditioning for clients.

Some of our most dramatic improvements have been in patients with neurological disorders, particularly Parkinson’s disease.  Ed has made reference to one of his favorite clients that came to us with fairly advanced Parkinson’s disease.  When she first came to us, she had difficulty navigating the threshold to our front door.  Now she brags about hiking trips and vacations where she carries her own luggage.  One of her proudest achievements was lifting her carry-on bags into the overhead bin (something she had been unable to do for years).  This is particularly meaningful to me as my father developed Parkinson’s when he was but 50 years old and suffered a gradual, but debilitating decline that finally took his life in 2004.  It is nothing short of amazing to watch someone with fairly advanced disease carry on as well, or better, than their age-matched cohorts.

The following article highlights the incredible impact that high intensity exercise has for those with Parkinson’s disease.

J Appl Physiol (1985). 2014 Jan 9. [Epub ahead of print]

NOVEL, HIGH-INTENSITY EXERCISE PRESCRIPTION IMPROVES MUSCLE MASS, MITOCHONDRIAL FUNCTION, AND PHYSICAL CAPACITY IN INDIVIDUALS WITH PARKINSON’S DISEASE.

Abstract

We conducted, in persons with Parkinson’s disease (PD), a thorough assessment of neuromotor function and performance in conjunction with phenotypic analyses of skeletal muscle tissue, and further tested the adaptability of PD muscle to high-intensity exercise training. Fifteen participants with PD (Hoehn & Yahr stage 2-3) completed 16 wk of high-intensity exercise training designed to simultaneously challenge strength, power, endurance, balance, and mobility function. Skeletal muscle adaptations (p<0.05) to exercise training in PD included: myofiber hypertrophy (type I:+14%, type II:+36%); shift to less fatigable myofiber type profile; and increased mitochondrial complex activity in both subsarcolemmal and intermyofibrillar fractions (I: +45-56%, IV: +39-54%). These adaptations were accompanied by a host of functional and clinical improvements (p<0.05): total body strength (+30-56%); leg power (+42%); single leg balance (+34%); sit-to-stand motor unit activation requirement (-30%); 6-min walk (+43m), Parkinson’s Disease Quality of Life Scale (PDQ-39, -7.8pts); Unified Parkinson’s Disease Rating Scale (UPDRS) total (-5.7pts) and motor (-2.7pts); and fatigue severity (-17%). Additionally, PD subjects in the pre-training state were compared to a group of matched, non-PD controls (CON; did not exercise). A combined assessment of muscle tissue phenotype and neuromuscular function revealed a higher distribution and larger cross sectional area of type I myofibers, and greater type II myofiber size heterogeneity in PD vs. CON (p<0.05). In conclusion, persons with moderately advanced PD adapt to high-intensity exercise training with favorable changes in skeletal muscle at the cellular and subcellular levels that are associated with improvements in motor function, physical capacity, and fatigue perception.

KEYWORDS:

Parkinson’s disease, high-intensity exercise, mitochondria, muscle hypertrophy, resistance training

For now, comments will remain off.  I am currently busy with multiple projects.  I will turn comments back on at a later date.

Comments are back up.  Here is a photo from yesterday’s workout.

Calf exercise on the MedX Leg Press

This week’s WOW was performed down at Ultimate Exercise and was focused on chest, back and neck.  Wendy did her every 14th day Big 4 and the kids each did a Big 3 workout.  The volume and intensity felt spot on (I quite immediately at failure…no deep inroad) and today I feel pleasantly sore, but energized.  My WOW is as follows:

SuperSlow Systems Pulldown, MedX Chest Press, Nautilus Pullover with SS retrofits, MedX Chest Press (vertical handles with adduction squeeze), SS Systems Neck Flexion, MedX Compound Row with SS cam, SS Systems Neck Extension.

Wendy did:

MedX Chest Press, SuperSlow Systems Pulldown, MedX Overhead Press, MedX Leg Press, TSC Neck Flex/Ext

The Kids did MedX Leg Press, MedX Chest Press and SS Systems Pulldown.

This week I am still hooked on myokines, but this time from a public health standpoint.  Ever since I have been in medical school, there has been a huge push for public health screening.  This has been driven by medical specialty societies, government agencies and the media.  The Susan G. Komen foundation has been hugely influential in influencing breast cancer “awareness” and mammography screening, to the extent that you can’t watch a major sporting event without pink cleats, towels and ribbons.  Screening for colon cancer via colonoscopy got major support after Katy Couric’s husband tragically died of colon cancer in his early 40’s.  Not to be outdone by the ladies, the major men’s screening issue has been PSA testing for prostate cancer.  Behind all of these assumptions is the idea that early detection would save lives.  Over and over we hear the anecdotes… “thank god they found (and removed) that lump, polyp or nodule” or… “if only it had been picked up earlier, then he/she may have faired better or survived”.  These are all narratives that our brains like to generate when we try to make sense of events that may be random and tragic.  These narratives are what drive our efforts to detect and fight back unforeseeable events that lead to tragedy, whether it be cancer, terrorism or school shootings.  But once we are hip deep in this kind of activity, we must look at our efforts and ask: does it work?  Does taking our shoes off at the airport really help prevent terrorism? Or are we creating our own needle-in-the-haystack scenario?  Does our exposure to radiation, blood draws and fiber optics up our posterior actually ward off the random and the tragic?  To answer this question, let me offer some analysis from the Number Needed to Treat Website.  Click on each link to read the real data on medical screening.

www.thennt.com/nnt/screening-mammography-for-reducing-deaths/

www.thennt.com/nnt/psa-test-to-screen-for-prostate-cancer/

www.thennt.com/nnt/ct-scans-to-screen-for-lung-cancer/

The problem with screening that becomes more and more sensitive is that it detects lesions that may never end up causing true disease.  Each of us carries nests of cancer cells all over our body.  The vast majority of times these cells are destroyed by immune surveillance and apoptosis (cell suicide) triggered by chemical messengers.  Research is starting to show that myokines may be a major force against nascent cancer cells.  Check out this article discussing the role of myokines in warding off colon cancer.

Gut. 2013 Jun;62(6):882-9. doi: 10.1136/gutjnl-2011-300776. Epub 2012 Jul 31.

A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise.

Aoi W, Naito Y, Takagi T, Tanimura Y, Takanami Y, Kawai Y, Sakuma K, Hang LP, Mizushima K, Hirai Y, Koyama R, Wada S, Higashi A, Kokura S, Ichikawa H, Yoshikawa T.

Author information

Abstract

OBJECTIVE:

Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some exercise-induced health benefits including metabolic improvement and anti-inflammatory effects in organs. The purpose of this study was to identify new myokines that contribute to the prevention of colon tumorigenesis.

METHODS:

To identify novel secreted muscle-derived proteins, DNA microarrays were used to compare the transcriptome of muscle tissue in sedentary and exercised young and old mice. The level of circulating secreted protein acidic and rich in cysteine (SPARC) was measured in mice and humans that performed a single bout of exercise. The effect of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion and function of SPARC was examined in culture experiments.

RESULTS:

A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells.

CONCLUSIONS:

These findings suggest that exercise stimulates SPARC secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by increasing apoptosis.

Next, check out this study that shows how myokines inhibit the proliferation of breast cancer cells.

Am J Physiol Endocrinol Metab. 2011 Sep;301(3):E504-10. doi: 10.1152/ajpendo.00520.2010. Epub 2011 Jun 7.

Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth.

Hojman P, Dethlefsen C, Brandt C, Hansen J, Pedersen L, Pedersen BK.

Author information

Abstract

Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.

With the scientific data that is accumulating, I think there needs to be a shift in public health efforts.  Rather than relying on early detection and medical intervention, we need to rely on lifestyle modifications that probably make detection of these tiny lesions irrelevant.  With the right lifestyle approach, we might never need to subject ourselves to the terror of a false-positive or the agony of the invasive procedures that follow.  Perhaps such hypersensitive screening can be used as a research tool to follow the natural course of these lesions with and without lifestyle interventions.  I suspect that we will find that the vast majority of these finds never result in clinically significant disease.  As we study meaningful strength exercise, I think we may find that the apoptosis of these lesions is more rapid and certain in those that invoke strength exercise.  Most importantly, I think there needs to be a major public health focus to determine if strength exercise might serve as the major preventative health intervention for all categories of disease.  Why cure cancer when you can prevent it?

Post your WOW’s and your thoughts (that are relevant to this post).


After being on a 5 way split for some time, I feel that my recovery has been fully replenished.  Twenty-five or more days between a given session was starting to feel like too long, especially for legs.  Also, as recovery returned, the lack of a systemic effect from engaging only a specific muscle group seemed to become more and more of a missing element.  So now I will gradually revert back to more body parts and a total body emphasis.  For instance I did shoulders/arms together and added a barbell squat at the end.  The squat was high rep and sub-failure, but was done to entrain a greater systemic effect.  Here is my legs/abs workout from yesterday (done at Fike).

Calf Exercise

Leg Extension

Leg Curl

Barbell Squat (135/52 reps for my 52 years on Earth.  After 25 reps I would rest-pause after every 5 reps until I reached my total)

Then I did sub-failure chin (10 reps) and dip (12 reps) just for a little “whole body effect”.

That afternoon I had a major nap (the kind where you wake yourself with your own snoring).  Last night I slept great and today I feel great despite the squat insanity.

This week I would like to bring a review article on another benefit of strength exercise that goes beyond cosmetics….Heat Shock Proteins (HSP).  Heat shock proteins are proteins that are transcribed in skeletal muscle in response to exercise (more specifically, contractile activity).  Contrary to their name, heat is not necessarily what entrains their production, although internal heat accumulation can contribute.  These proteins help to speed the repair of exercise-induced muscle damage and once present they not only help you to be more resilient to exercise stress, they help to protect and repair from other types of injury and insults.  HSP’s are thought to be a major determinant in whether patients survive during bouts of sepsis, trauma or severe burns.   One of the reasons these proteins are named Heat Shock proteins is that they help to prevent rhabdomyolysis that can occur during hot weather exertion.  However, don’t be confused and think that doing Crossfit in the desert is the best way to induce HSP production.  Such an approach is totally not necessary. Just because something works in one direction, doesn’t mean that it is required in the other direction.  As the article states, HSP are not just protective against cellular damage, but are thought to be involved in cell signaling that affect metabolism and health in ways remaining to be discovered.  Currently, exercise is being considered a corrective, non-pharmocologic therapy for protein-folding diseases and aging itself.  As research in the area of myokines and HSP’s expands, I believe strength exercise will emerge as the predominant non-pharmacologic intervention in almost any disease state.  Here is the abstract.  Sorry I couldn’t post the full article.  The SpringerLink is $49.95 and is copywrited.

Sports Med. 2009;39(8):643-62. doi: 10.2165/00007256-200939080-00003.

The exercise-induced stress response of skeletal muscle, with specific emphasis on humans.

Abstract

Skeletal muscle adapts to the stress of contractile activity via changes in gene expression to yield an increased content of a family of highly conserved cytoprotective proteins known as heat shock proteins (HSPs). These proteins function to maintain homeostasis, facilitate repair from injury and provide protection against future insults. The study of the exercise-induced production of HSPs in skeletal muscle is important for the exercise scientist as it may provide a valuable insight into the molecular mechanisms by which regular exercise can provide increased protection against related and non-related stressors. As molecular chaperones, HSPs are also fundamental in facilitating the cellular remodelling processes inherent to the training response. Whilst the exercise-induced stress response of rodent skeletal muscle is relatively well characterized, data from humans are more infrequent and less insightful. Data indicate that acute endurance- and resistance-type exercise protocols increase the muscle content of ubiquitin, alphaB-crystallin, HSP27, HSP60, HSC70 and HSP70. Although increased HSP transcription occurs during exercise, immediately post-exercise or several hours following exercise, time-course studies using western blotting techniques have typically demonstrated a significant increase in protein content is only detectable within 1-2 days following the exercise stress. However, comparison amongst studies is complicated by variations in exercise protocol (mode, intensity, duration, damaging, non-damaging), muscle group examined, predominant HSP measured and, perhaps most importantly, differences in subject characteristics both within and between studies (training status, recent activity levels, nutritional status, age, sex, etc.). Following ‘non-damaging’ endurance-type activities (exercise that induces no overt structural and functional damage to the muscle), the stress response is thought to be mediated by redox signalling (transient and reversible oxidation of muscle proteins) as opposed to increases in contracting muscle temperature per se. Following ‘damaging’ forms of exercise (exercise that induces overt structural and functional damage to the muscle), the stress response is likely initiated by mechanical damage to protein structure and further augmented by the secondary damage associated with inflammatory processes occurring several days following the initial insult. Exercise training induces an increase in baseline HSP levels, which is dependent on a sustained and currently unknown dose of training and also on the individual’s initial training status. Furthermore, trained subjects display an attenuated or abolished stress response to customary exercise challenges, likely due to adaptations of baseline HSP levels and the antioxidant system. Whilst further fundamental work is needed to accurately characterize the exercise-induced stress response in specific populations following varying exercise protocols, exercise scientists should also focus their efforts on elucidating the precise biological significance of the exercise-induced induction of HSPs. In addition to their potential cytoprotective properties, the role of HSPs in modulating cell signalling pathways related to both exercise adaptation and health and disease also needs further investigation. As a non-pharmacological intervention, exercise and the associated up-regulation of HSPs and the possible correction of maladapted pathways may therefore prove effective in providing protection against protein misfolding diseases and in preserving muscle function during aging.

Post Your WOW’s and your thoughts on this topic.  Please stay proximal to the topic.  I want to keep this a more of a blog and less of a discussion forum.

I apologize for the delay in posting, but my work schedule has been quite hectic.  I did the following WOW yesterday at UE after a busy ER shift.  Wendy and the kids met me and worked out also.

SuperSlow Systems Pulldown

Nautilus Pullover with SS retrofits

MedX Compound Row with SS retrofit fall-off cam

SuperSlow Systems Neck Extension

Barbell Deadlift

Wendy did her every 14th day workout.  She has reverted back to her Big 4, feeling that the rotating specialization routines did not offer her any advantage.  Her routine was (MedX chest press, SSS Pulldown, MedX overhead press and MedX leg press).  The kids both do a Big 3 routine of Leg Press, Chest Press and Pulldown.

Lately I have found myself hooked on the literature surrounding myokines.  I am amazed at the degree of endocrine activity and cross-talk with other tissues that is exhibited by skeletal muscle.  I have always had the sense that skeletal muscle and the activities that result in its activity and adaptations have always had health benefits that go way beyond strength or “gettin ’swole”.  But as I delve into the literature on myokines, I must admit….I had no idea!  Marc P wanted to discuss strength training’s contribution to fat loss.  Myokines are where most of this action takes place.  There are mediators that enhance fatty acid oxidation in the mitochondria, others accelerate the mobilization of glycogen from the muscle while simultaneously up-regulating insulin receptors and lowering serum insulin levels (effectively reversing the obesogenic effects of the metabolic syndrome).  Myokines also directly oppose the inflammatory cytokines produced by adipose tissue and help to block uptake of fat into the adipocyte.  There are myokines that bind monocytes and T-cells that help to repair muscle damage, but also attack foreign invaders and trigger apoptosis of cancer cells.  In one of the studies listed, a specific myokine liberated from skeletal muscle during exercise was shown to halt the growth of breast cancer cells and even caused apoptosis (cell destruction) of breast cancer cells.  A perusal of this review article, along with the attached citations will show a virtual treasure-trove of benefits that are derived when skeletal muscle is engaged in a challenging way.

These articles also indicate that all fiber types secrete beneficial myokines and that slow twitch oxidative, intermediate and fast twitch fibers all secrete different myokines, each with their beneficial effect.  Despite the recent emphasis on the importance of the fast twitch fibers, it seems that all fiber types have something to contribute.  In my opinion, this means that endurance exercisers may show a different myokine profile from those that emphasize strength and power.  I suspect, however, that it is possible to have the best of all worlds with regard myokines if you participate in a combination of exercise routines that cover all fiber types or better yet…if you use an exercise protocol that results in sequential recruitment of all fiber types.

What is most evident to me is that what matters most is that the populace at large needs to participate in meaningful exercise.  My major concern about some of the heated debate that goes on here about what is “best” my make a “newbie” visiting the site decide to throw up their hands and not get started at all.  Sometimes our arguments can make this look way more complex than it needs to be for someone who needs nothing more than to get started.  So for any newcomers who have been intimidated by the technical verbiage and heated debates, please understand that ALL who participate here are deriving the amazing benefit of myokines and that the techincal discussion and debate is just icing on the cake that keeps us all interested and in the game.  Remember….Just. Lift. Weights.  Get started.  As you progress and experiment, then you can join the fray.  But rest assured, whether you are working out on state of the art RenEx machines under professional supervision, or if you are lifting an old barbell in your garage or basement you are part of an elite club that knows the amazing value of myokines.  I have attached the full-text article below.  Please read it and be proud of what we promote here.

Adipocyte. 2012 July 1; 1(3): 164–167.
PMCID: PMC3609091

Muscle-to-organ cross talk mediated by myokines

Abstract

Cytokines and other peptides are secreted from skeletal muscles in response to exercise and function as hormones either locally within the muscle or by targeting distant organs. Such proteins are recognized as myokines, with the prototype myokine being IL-6. Several studies have established a role of these muscle-derived factors as important contributors of the beneficial effects of exercise, and the myokines are central to our understanding of the cross talk during and after exercise between skeletal muscles and other organs. In a study into the mechanisms of a newly defined myokine, CXCL-1, we found that CXCL-1 overexpression increases muscular fatty acid oxidation with concomitant attenuation of diet-induced fat accumulation in the adipose tissue. Clearly this study adds to the concept of myokines playing an important role in mediating the whole-body adaptive effects of exercise through the regulation of skeletal muscle metabolism. Yet, myokines also contribute to whole-body metabolism by directly signaling to distant organs, regulating metabolic processes in liver and adipose tissue. Thus accumulating data shows that myokines play an important role in restoring a healthy cellular environment, reducing low-grade inflammation and thereby preventing metabolic related diseases like insulin resistance and cancer.

Keywords: cancer, diabetes, exercise, myokine, physical activity

Exercise is associated with many beneficial metabolic and health effects. Today it is known that during exercise, cytokines and other peptides are secreted by the working muscles with the potential to act locally within the muscle tissue or in an endocrine manner by targeting distant organs. Although they are not exclusively secreted by the muscle cells, such proteins are classified as “myokines” within the context of skeletal muscle physiology.1 Emerging evidence suggests that these muscle-derived cytokines play an important role in mediating both acute exercise-associated metabolic changes, as well as the metabolic changes following training adaptation.2 Increased insulin responsiveness, glucose uptake and fatty acid oxidation within skeletal muscles are some of the anticipated beneficial effects of regular exercise, all of which have been shown in part to be mediated by myokines. Likewise, systemic effects of myokines released in response to muscle contractions are involved in various immediate and long-term metabolic regulatory mechanisms in distant organs like the adipose tissue.3 Thus myokines are central to our understanding of the cross talk during and after exercise between skeletal muscles and other organs (Fig. 1). In view of that, further insight into the effect and regulation of potential myokines is of major importance.

figure adip-1-164-g1

Figure 1. Muscle-organ cross talk mediated by myokines. In response to muscle contraction skeletal muscle expresses and releases myokines into the circulation. The myokines mediate effects locally within the muscle in an autocrine or paracrine

The first myokine identified was interleukin 6 (IL-6),4 which is now recognized as the prototype myokine, exerting both local muscular effects as well as endocrine effects on distant organs.5 Since the discovery of IL-6, it has been recognized that skeletal muscle has the capacity to express a large range of myokines. Today the list of verified myokines includes IL-6, IL-8, IL-15, brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), fibroblast growth factor 21 (FGF21) and follistatin-like-1.3 In addition, recent proteomic studies have predicted that the list of myokines may include more than 600 candidates belonging to distinctly different protein families.6 Recently we and others reported that an acute bout of exercise in mice induced a 6-fold increase in skeletal muscle mRNA and a 2.4-fold increase in serum concentration of the chemokine CXC motif ligand-1 (CXCL-1) also known as KC (keratinocyte-derived chemokine), suggesting that CXCL-1 acts as an exercise-induced myokine.7,8Murine CXCL-1 is often mentioned as the functional homolog to human IL-8, which previously was identified as a myokine in humans.9 However, murine CXCL-1 shares the highest sequence homology (90% homology in conserved regions) with human CXCL-1, also named GROα (growth-related oncogene, α).10 CXCL-1 belongs to the glutamate-leucine-arginine (ELR)-containing CXC chemokine family and has primarily received attention for its role in inflammation, chemotaxis and angiogenesis,11,12 its neuro-protective effects13 and as a regulator of tumor growth14,15 whereas its role in metabolism remains to be clarified.

In line with the involvement of myokines in regulation of skeletal muscle metabolism, we went on to characterize the role of CXCL-1 in the exercise-associated adaptations in oxidative capacity in the muscle.16 To this end, we used a mouse model of in vivo electrotransfer-mediated overexpression of CXCL-1 in the tibialis cranialis muscle. The resulting increases in muscle CXCL-1 mRNA and serum CXCL-1 in this model are within the normo-physiological range and comparable to levels observed in response to a single bout of exercise.7,8 Importantly this model reflects the long-term effects of regular exercise-induced peaks in CXCL-1 rather than an occasional acute exercise effect. As assessed by MR scanning, DEXA scanning and weight of dissected organs, this long-term overexpression model revealed a CXCL-1-dependent reduction in the diet-induced fat accumulation in adipose tissue. In fact, after three months of high-fat feeding, CXCL-1 transfected animals had a significantly lower visceral fat mass (1277.5 ± 107.2 mg) compared with control mice (1889.5 ± 147.1 mg, p < 0.01). Likewise, did these mice have lower subcutaneous fat mass (494.8 ± 51.2 mg) compared with control mice (637.2 ± 40.8 mg, p < 0.05). Chow-fed mice also had lower levels of adipose tissue. As determined by DEXA scanning eight weeks after the transfection, the CXCL-1 transfected mice had significantly lower proportion of total body fat (13.2 ± 1.6%) compared with chow-fed control mice (19.8 ± 1.5%, p < 0.01). Similar results were found by MR scanning. Interestingly, the reduced accumulation of fat in the CXCL-1 transfected animals was associated with increased fatty acid oxidation in the muscles, as measured both directly and indirectly through upregulation of rate-limiting oxidative enzymes. Furthermore, the CXCL-1-dependent reduction adipose tissue mass was accompanied by whole-body improvements in glucose tolerance and insulin sensitivity. Clearly this study shows that by influencing metabolism locally in the muscles, the myokines are likely to be involved in the whole-body metabolic adaptive changes that occur in response to regular exercise like, for example, attenuation of fat accumulation.

Induction of other myokines, in particular IL-6, has been involved in similar metabolic adaptations. By signaling through the gp130Rβ/IL-6Rα receptor, causing subsequent activation of the AMPK and/or phosphatidylinositol 3-kinase (PI3-kinase) pathways, IL-6 acts within the muscle to increase glucose uptake and fatty acid oxidation.1 Upon receptor activation, IL-6 signals through either the Janus kinase/signal transducer and activator of transcription (STAT) pathway or a Ras/ERK/CAAT enhancer binding protein (C/EBP) β pathway.17

In addition to the local muscular effects that indirectly affect whole body metabolism, myokines have also been shown to act directly on distant organs when released into the systemic circulation. Again IL-6 can be used as an example. Following release from both type I and type II muscle fibers in response to muscle contractions circulating IL-6 works in an endocrine fashion.1 In adipose tissue IL-6 has been shown to increase lipolysis and fatty acid oxidation,18 likely through the induction of AMPK phosphorylation.19 In further support of IL-6 affecting accumulation of fat in adipose tissue, IL-6 knockout mice have been found to develop late-onset obesity.20 In the liver, muscle-derived IL-6 is suggested to enhance hepatic glucose production during exercise21 and has been reported to directly upregulate gluconeogenic genes, i.e., phosphoenolpyruvate carboxykinase (PEPCK) and 6-phosphatase (G6Pase), leading to increased hepatic glucose production.22 Interestingly, IL-6 is also thought to affect pancreatic function, and secretory products from skeletal muscles have directly been shown to increase proliferation and glucose-stimulated insulin secretion from primary β-cells.23,24 In addition, injection of IL-6 as well as elevated levels of IL-6 induced by exercise have recently been demonstrated to stimulate GLP-1 secretion from intestinal L cells and pancreatic α cells, leading to improvements in insulin secretion and glycemia.25 Thus, skeletal muscle and the pancreas act in a synergistic manner to monitor systemic glucose homeostasis and these results demonstrate a role of myokines in mediating cross talk between insulin sensitive tissues.

In line with this, plasma IL-6 is not only directly correlated with exercise intensity, but is also inversely related to plasma glucose level.26 With this, it is thought that IL-6 works as a sensor of carbohydrate availability.18,22,27 Thus, contracting muscle fibers produce and release IL-6 in an endocrine manner to facilitate substrate mobilization from liver and adipose tissue. More recently it was also reported that muscle-derived IL-6 induces expression of CXCL-1 in the liver and that IL-6 is directly essential for the peaks in liver CXCL-1 expression that occurs in response to exercise. These observations further suggest that IL-6 is involved in muscle-to-liver cross talk during exercise.8 Also, an exercise-induced and PGC1-a (transcriptional co-activator PPAR-γ co-activator-1 α) dependent myokine named Irisin was recently reported to replicate some of the positive effects of exercise and diet. It increases energy expenditure likely through stimulation of UCP-1 and brown-fat-like development and was found to improve glucose tolerance in obese animals.28

Definitely the communication network between muscles and other tissues define a physiological concept of muscle-to-organ cross talk. Common for many of the identified myokines are a direct or indirect effect on adipose tissue. Importantly, visceral fat is known as a source of systemic chronic low-grade inflammation, which in turn is involved in the pathogenesis of various disorders like insulin resistance, atherosclerosis and cancer.5 The attenuating effect of myokines on accumulation visceral adipose tissue either by acting directly on the adipose tissue itself or by improving fatty acid metabolism in the muscle is therefore of major importance in describing why inactivity is a strong risk factor for development of various diseases induced by low-grade inflammation like type 2 diabetes and cancer.5 With this, the myokines could in theory be therapeutic for human metabolic disease and other kind of disorders that normally are improved with regular exercise.

In continuation of this, regular exercise is clearly associated with reduced cancer development and progression in large epidemiological studies29,30 and a few animal studies report that exercise is associated with decreased tumor growth and metastatic dissemination.31 The protective effect of exercise is applicable on a diverse array of neoplastic diseases, indicating that the mechanism behind this protection is not limited by specific oncogenic mutations but likely caused by more general mechanisms. We have recently shown that myokines, in addition to the reduction of low-grade inflammation, also play a direct role in the tumor-suppressing effect of exercise. By incubating breast cancer cells with serum taken immediately after an exercise bout, we found that the exercise-conditioned serum could reduce cancer cell viability and induce apoptosis through caspase activation.32 This study identified Oncostatin M as an exercise-induced myokine with anti-proliferative effects on the breast cancer cells. Likely the protection of exercise on tumor development and progression occurs through a variety of exercise-related changes like improved inflammatory fitness, immune function, growth factor signaling, sex hormones and improved metabolic status some of which are affected by the myokines. Knowing the mechanisms behind the beneficial anti-cancer effect of exercise will serve as foundation for public health guide with regard to exercise and likely facilitate the improvement of current anti-cancer strategies

Taken together, with the identified pleiotropic effects of myokines on multiple tissues, leading to fine-tuning of fuel utilization and energy homeostasis in these tissues, we believe that these secreted myokines are able to restore a healthy cellular environment, reduce low-grade inflammation and thereby prevent metabolic related diseases like insulin resistance and cancer.

Acknowledgments

The Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National Research Foundation (02-512-55). This study was further supported by the Danish Medical Research Council, the Commission of the European Communities (grant agreement 223576-MYOAGE) and by grant from The Novo Scholarship Program 2010.

Notes

Pedersen L, Olsen CH, Pedersen BK, Hojman P. Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle Am J Physiol Endocrinol Metab 2012 302 E831 40 doi: 10.1152/ajpendo.00339.2011.

Footnotes

Reference

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