Friday, October 31, 2008

Morphological Hypertrophic Muscle Adaptations (aka “I Wanna Get Hyoooge!!”)

Morphological Hypertrophic Muscle Adaptations (aka, Mechanisms Behind “I Wanna Get Hyoooge!!”)

Pop your head into just about any gym in America, and observe the male population (especially the younger ones) train. While the training methods are interesting in themselves, the common battle cry of the young Arnold wannabes is usually the same “I Wanna Get Hyoooge.” In an effort to explore the mechanisms behind the scenes in the body to help out these “bros” it is time to board the magical muscle mystery tour. Tour stops include a drive by of the nervous system, muscle fiber types, and how muscles adapt to exercise to get bigger and badder (as in a Michael Jackson “bad” is now good way).

Before we dive in head first into this, we need to do a short little anatomy tour. They say a picture is worth a thousand words, so check out figure below.

This time around I will spare you all the details on the exact names of each, but notice how a single fiber at the end goes into another group of fibers and then THAT group goes into another group until we are all the way up to the muscle itself. Muscle fibers can be broadly defined as type2 fast twitch or type 1 slow twitch (8). Fast twitch (type 2) fibers can produce more force, but they don’t last as long (26). Think of an NFL lineman. He can produce a ton of force to knock you into next week, but it is unlikely he will be chasing your around the block or very far at all. Type 2 (slow twitch) muscle fibers are like the slower cousin to the type 2, think energizer bunny. They can’t produce as much force, but they keep going and going and going and going………..

Remember that the nervous system is the head cheese, numero uno, el presidente, the commander in charge that controls all muscle movements. The nervous system also controls which fibers are type 1 or 2! Buller et al. (9) in 1960, carefully did the ole “switcheroo” on cats and switched nerves and a type 2 muscle fiber with a new type 1 NERVE now took on the properties of a type 1 muscle fiber! Think of this as “what the commander says goes.”
Another key point is that “living systems are build up through use and atrophy (get smaller) with disuse.” So when you are in the gym blasting away, you are actually making your muscle SMALLER! Yikes! The good part is that your body responds by BUILDING up those damaged fibers during the recovery period (33). So next time you do a similar exercise, the body has “new and improved” muscle tissue to better handle the damage. Pretty sweet!

Muscle Growth Time
Skeletal muscle is a very dynamic tissue capable of adapting to the stress placed on it. The process of exercise-induced adaptation in skeletal muscle involves a multitude of signaling mechanisms all the way down to the genetic level, ultimately putting together strings of amino acids to form new proteins in the form of more muscle tissue (10). Whooo ha, and the gym “bros” rejoice!

As mentioned, muscle growth is commonly referred to as “hypertrophy” (34) or more accurately as an increase in muscle fiber SIZE. How does this happen? While a complete answer to that question is beyond this short article, what do you think are some key processes? “TESTOSTERONE!” Good guess and there is a fair amount of data to support this (16, 17, 29, 30), there is also data (although less) to show that in castrated (denutted—youch!!!) animals (yeah I know it was not done in humans but do you want to volunteer for those studies?) are still able to increase muscle size despite having testosterone levels at very low levels (22, 24). “NUTRITION!” Yes, there is no denying that nutrition especially extra calories and protein are needed for muscle hypertrophy (11, 13, 19) but even in caloric restriction muscles can still get bigger (12). “INSULIN!” While insulin is the most anabolic (building) hormone in the body, it is not required either (7). (Side note, I am using the term “anabolic” in the physiologic sense where it is taking small things and making bigger things with them. This can be proteins into new muscle or fatty acids into new fat storage around your waist. And yes, too much insulin can make you a fat bastard). So the muscle building process is a complicated one.

How Do These Genes Look
Further down the hole, we have a whole slew of molecular signaling guys, some newly discovered like Mighty that can dramatically influence muscle growth. Mighty is a downstream metabolite of myostatin. Most have probably heard of myostatin now or seen the huge picture of the Belgium Bull.

Belgian Blue Bulls (say that fast three times in a row) have a mutation in the myostatin gene that produces a truncated, ineffective form of the protein (20), so in English there is almost no myostatin hanging around. The absence of myostatin allows unchecked muscle growth and interferes with fat deposition; the result is a lean, “double-muscled” bull. Yikes! Remember that LESS myostatin = MORE muscle.

The new kid on the block now is Mighty. Mighty is expressed in a variety of different tissues but appears to be specifically regulated by myostatin in skeletal muscle. Overexpression of Mighty in certain cells (ok, C2C12 cells if you really want to know) results in enhanced and accelerated differentiation and hypertrophy of myotubes (this is good for muscle growth, trust me) and leads to increased and earlier expression of MyoD and insulin like growth factor II (IGF-II) (both are good for muscle growth) (23).

Enough Biochem Yacking already
So I spared you from a detailed talk on Interleukin-4 (IL-4) and interleukin-13 (IL-13) that are involved in getting hyoooge (27), so be thankful! Watch out—Geek alert! Serrano et al. (28) recently showed a role for IL-6 in hypertrophic muscle growth and provide mechanistic evidence for the contribution of satellite cells to this process, in our fury friends the mouse.

So back to our irregularly scheduled program. So far we know 1) nutrition is key-calories and protein are needed to build muscle 2) we need a stimulus—weight training works well here (31) 3) certain hormonal and biochemical changes need to take place—from hormonal changes down to even the molecular level.
Shut Up Already and Tell Me HOW to Get Hyoooooooooge!
During short term studies of less than 10 weeks, it was shown that type 2 fibers hypertrophy (get bigger) much faster from training than their slow cousins the Energizer bunny type 1 fibers (1). MacDougall et al.(21) however investigated a longer time period of 5–6 months of heavy resistance training (weight lifting) in seven males and demonstrated a significant cross sectional increase in type 2 AND type 1 fibers; so long term it appears that BOTH fiber types can increase in size. Take home message, use a wide variety of reps.

Damage Plan
The goal of some dedicated Arnold wannabes is to destroy tissue! No pain no gain! Go hard or go home! Is there any research to support this method if we can get hyoooooooooge? There is actually some evidence to support this notion. Goldspink about 30 years ago proposed that if you literally tear the muscle fiber in half (these would be very small tears of course), that this may promote splitting of the muscle fibers once the body goes to work repairing those fibers; thus resulting in more fibers over time. More fibers= more size. The fancy word associated with increasing muscle fiber NUMBER is hyperplasia. The downside is that this phenomena is highly debatable with virtually the studies being conducted on animals (primarily cats and birds), so how it applies to humans is not currently known (2-6, 15, 18, 32).

We know that eccentric (lowering a heavy weight) can scramble the muscle fibers (induce lots of damage) and it appears that fiber disruption induced by habitual weightlifting exercise is essentially repaired after 5 days of inactivity in trained men (14) and oxidative stress indices changed significantly with most peaking at 48 hours (25).

What does any of this mean?
Although data is somewhat limited on the “destroy tissue” approach in relation to hypertrophy there is enough to support the idea for muscle hypertrophy, but keep in mind that your recovery time may be longer with this approach. Your muscles get bigger OUTSIDE the gym when they are repairing!

Thus ends our very brief ride on the magically, muscle mystery tour! I hoped you have enjoyed the tour and kept your hands inside the bus at all times. We got to spend some time in the land of the nervous system, fiber types, stimulus for adaptation (aka weight training), and the adaptation process itself. The take away is that muscle hypertrophy is a complicated process and our best bet in the quest for huge-dom is 1) excellent nutrition with a surplus of calories and proteins and 2) consistent weight training with adequate time for recovery; especially if eccentric movements are used to induce muscle damage.
Time to get to the gym!

Mike T. Nelson has a BA in Natural Science, a MS in Mechanical Engineering (Biomechanics) and is currently a PhD student in Kinesiology (Exercise Physiology) at the University of Minnesota. His research interests are on the effects of energy drinks on metabolic health and the nervous system.

1. The effect of weight-lifting exercise related to muscle fiber composition and muscle cross-sectional area in humans. Eur J Appl Physiol. . 1979; 40(2):95.
2. Antonio J, WJ Gonyea. Muscle fiber splitting in stretch-enlarged avian muscle. Med Sci Sports Exerc. . 1994; 26(8):973-7.
3. Antonio J, WJ Gonyea. Progressive stretch overload of skeletal muscle results in hypertrophy before hyperplasia. J Appl Physiol. . 1993; 75(3):1263-71.
4. Antonio J, WJ Gonyea. Role of muscle fiber hypertrophy and hyperplasia in intermittently stretched avian muscle. J Appl Physiol. . 1993; 74(4):1893-8.
5. Antonio J, WJ Gonyea. Role of muscle fiber hypertrophy and hyperplasia in intermittently stretched avian muscle. J Appl Physiol. . 1993; 74(4):1893-8.
6. Antonio J, WJ Gonyea. Skeletal muscle fiber hyperplasia. Med Sci Sports Exerc. . 1993; 25(12):1333-45.
7. Bolster DR, LS Jefferson, SR Kimball. Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling. Proc Nutr Soc. . 2004; 63(2):351-6.
8. Brooks GH, TD Fahey, Baldwin, Kenneth David Sutherland. Exercise physiology: human bioenergetics and its applications. Boston : McGraw-Hill, c2005.; 2005. p. 22.
9. BULLER AJ, JC ECCLES, RM ECCLES. Interactions between motoneurones and muscles in respect of the characteristic speeds of their responses. J Physiol. . 1960; 150:417-39.
10. Coffey VG, JA Hawley. The molecular bases of training adaptation. Sports Med. . 2007; 37(9):737-63.
11. Cribb PJ, AD Williams, CG Stathis, MF Carey, A Hayes. Effects of whey isolate, creatine, and resistance training on muscle hypertrophy. Med Sci Sports Exerc. . 2007; 39(2):298-307.
12. Donnelly JE, T Sharp, J Houmard, et al. Muscle hypertrophy with large-scale weight loss and resistance training. Am J Clin Nutr. . 1993; 58(4):561-5.
13. Dreyer HC, MJ Drummond, B Pennings, et al. Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab. . 2008; 294(2):E392-400.
14. Gibala MJ, SA Interisano, MA Tarnopolsky, et al. Myofibrillar disruption following acute concentric and eccentric resistance exercise in strength-trained men. Can J Physiol Pharmacol. . 2000; 78(8):656-61.
15. Giddings CJ, WJ Gonyea. Morphological observations supporting muscle fiber hyperplasia following weight-lifting exercise in cats. Anat Rec. . 1992; 233(2):178-95.
16. Herbst KL, S Bhasin. Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care. . 2004; 7(3):271-7.
17. Kadi F. Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement. Br J Pharmacol. . 2008; 154(3):522-8.
18. Kelley G. Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis. J Appl Physiol. . 1996; 81(4):1584-8.
19. Kerksick CM, B Leutholtz. Nutrient administration and resistance training. J Int Soc Sports Nutr. . 2005; 2:50-67.
20. Li ZB, HD Kollias, KR Wagner. Myostatin directly regulates skeletal muscle fibrosis. J Biol Chem. . 2008; 283(28):19371-8.
21. MacDougall JD, GC Elder, DG Sale, JR Moroz, JR Sutton. Effects of strength training and immobilization on human muscle fibres. Eur J Appl Physiol Occup Physiol. . 1980; 43(1):25-34.
22. Mackova EV, P Hnik. Some hormonal factors (hypophysectomy, castration and testosterone administration) modifying the course of "compensatory" muscle hypertrophy in the rat. Physiol Bohemoslov. . 1976; 25(4):325-32.
23. Marshall A, MS Salerno, M Thomas, et al. Mighty is a novel promyogenic factor in skeletal myogenesis. Exp Cell Res. . 2008; 314(5):1013-29.
24. Max SR, NE Rance. No effect of sex steroids on compensatory muscle hypertrophy. J Appl Physiol. . 1984; 56(6):1589-93.
25. Paschalis V, MG Nikolaidis, IG Fatouros, et al. Uniform and prolonged changes in blood oxidative stress after muscle-damaging exercise. In Vivo. . 2007; 21(5):877-83.
26. Powers SK, ET Howley. Exercise Physiology : Theory and Application to Fitness and Performance. McGraw-Hill Humanities/Social Sciences/Languages; 2006. p. 624.
27. Prokopchuk O, Y Liu, L Wang, K Wirth, D Schmidtbleicher, JM Steinacker. Skeletal muscle IL-4, IL-4Ralpha, IL-13 and IL-13Ralpha1 expression and response to strength training. Exerc Immunol Rev. . 2007; 13:67-75.
28. Serrano AL, B Baeza-Raja, E Perdiguero, M Jardi, P Munoz-Canoves. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. . 2008; 7(1):33-44.
29. Singh R, JN Artaza, WE Taylor, NF Gonzalez-Cadavid, S Bhasin. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. . 2003; 144(11):5081-8.
30. Sinha-Hikim I, SM Roth, MI Lee, S Bhasin. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. . 2003; 285(1):E197-205.
31. Spiering BA, WJ Kraemer, JM Anderson, et al. Resistance exercise biology : manipulation of resistance exercise programme variables determines the responses of cellular and molecular signalling pathways. Sports Med. . 2008; 38(7):527-40.
32. Taylor NA, JG Wilkinson. Exercise-induced skeletal muscle growth. Hypertrophy or hyperplasia? Sports Med. . 1986; 3(3):190-200.
33. Wernig A. Regeneration capacity of skeletal muscle. Ther Umsch. . 2003; 60(7):383-9.
34. Wilmore JH, DL Costill. Physiology of Sport and Exercise, Fourth Edition. Human Kinetics Publishers; 2007. p. 574.