The Mystery of Skeletal Muscle Hypertrophy
Richard Joshua Hernandez, B.S. and Len Kravitz, Ph.D.
Through exercise, the muscular work done against a progressively challenging overload leads to increases in muscle mass and cross-sectional area, referred to as hypertrophy. But why does a muscle cell grow and how does it grow? Although an intense topic of research, scientists still do not fully understand the complete (and very complex) picture of how muscle adapts to gradually overloading stimuli. In this article, a brief but relevant review of the literature is presented to better understand the multifaceted phenomenon of skeletal muscle hypertrophy.
What is Muscular Hypertrophy?
Muscular hypertrophy is an increase in muscle mass and cross-sectional area (1). The increase in dimension is due to an increase in the size (not length) of individual muscle fibers. Both cardiac (heart) and skeletal muscle adapt to regular, increasing work loads that exceed the preexisting capacity of the muscle fiber. With cardiac muscle, the heart becomes more effective at squeezing blood out of its chambers, whereas skeletal muscle becomes more efficient at transmitting forces through tendonous attachments to bones (1).
Skeletal muscle has two basic functions: to contract to cause body movement and to provide stability for body posture. Each skeletal muscle must be able to contract with different levels of tension to perform these functions. Progressive overload is a means of applying varying and intermittent levels of stress to skeletal muscle, making it adapt by generating comparable amounts of tension. The muscle is able to adapt by increasing the size and amount of contractile proteins, which comprise the myofibrils within each muscle fiber, leading to an increase in the size of the individual muscle fibers and their consequent force production (1).
The Physiology of Skeletal Muscle Hypertrophy
The physiology of skeletal muscle hypertrophy will explore the role and interaction of satellite cells, immune system reactions, and growth factor proteins (See Figure 1. for Summary).
Satellite cells function to facilitate growth, maintenance and repair of damaged skeletal (not cardiac) muscle tissue (2). These cells are termed satellite cells because they are located on the outer surface of the muscle fiber, in between the sarcolemma and basal lamina (uppermost layer of the basement membrane) of the muscle fiber. Satellite cells have one nucleus, with constitutes most of the cell volume.
Usually these cells are dormant, but they become activated when the muscle fiber receives any form of trauma, damage or injury, such as from resistance training overload. The satellite cells then proliferate or multiply, and the daughter cells are drawn to the damaged muscle site. They then fuse to the existing muscle fiber, donating their nuclei to the fiber, which helps to regenerate the muscle fiber. It is important to emphasize the point that this process is not creating more skeletal muscle fibers (in humans), but increasing the size and number of contractile proteins (actin and myosin) within the muscle fiber (see Table 1. for a summary of changes that occur to muscle fibers as they hypertrophy). This satellite cell activation and proliferation period lasts up to 48 hours after the trauma or shock from the resistance training session stimulus (2).
The amount of satellite cells present within in a muscle depends on the type of muscle. Type I or slow-twitch oxidative fibers, tend to have a five to six times greater satellite cell content than Type II (fast-twitch fibers), due to an increased blood and capillary supply (2). This may be due to the fact that Type 1 muscle fibers are used with greatest frequency, and thus, more satellite cells may be required for ongoing minor injuries to muscle.
As described earlier, resistance exercise causes trauma to skeletal muscle. The immune system responds with a complex sequence of immune reactions leading to inflammation (3). The purpose of the inflammation response is to contain the damage, repair the damage, and clean up the injured area of waste products.
The immune system causes a sequence of events in response to the injury of the skeletal muscle. Macrophages, which are involved in phagocytosis (a process by which certain cells engulf and destroy microorganisms and cellular debris) of the damaged cells, move to the injury site and secrete cytokines, growth factors and other substances. Cytokines are proteins which serve as the directors of the immune system. They are responsible for cell-to-cell communication. Cytokines stimulate the arrival of lymphocytes, neutrophils, monocytes, and other healer cells to the injury site to repair the injured tissue (4).
The three important cytokines relevant to exercise are Interleukin-1 (IL-1), Interleukin-6 (IL-6), and tumor necrosis factor (TNF). These cytokines produce most of the inflammatory response, which is the reason they are called the “inflammatory or proinflammatory cytokines” (5). They are responsible for protein breakdown, removal of damaged muscle cells, and an increased production of prostaglandins (hormone-like substances that help to control the inflammation).
Growth factors are highly specific proteins, which include hormones and cytokines, that are very involved in muscle hypertrophy (6). Growth factors stimulate the division and differentiation (acquisition of one or more characteristics different from the original cell) of a particular type of cell. In regard with skeletal muscle hypertrophy, growth factors of particular interest include insulin-like growth factor (IGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). These growth factors work in conjunction with each other to cause skeletal muscle hypertrophy.
Insulin-Like Growth Factor
IGF is a hormone that is secreted by skeletal muscle. It regulates insulin metabolism and stimulates protein synthesis. There are two forms, IGF-I, which causes proliferation and differentiation of satellite cells, and IGF-II, which is responsible for proliferation of satellite cells. In response to progressive overload resistance exercise, IGF-I levels are substantially elevated, resulting in skeletal muscle hypertrophy (7).
Fibroblast Growth Factor
FGF is stored in skeletal muscle. FGF has nine forms, five of which cause proliferation and differentiation of satellite cells, leading to skeletal muscle hypertrophy. The amount of FGF released by the skeletal muscle is proportional to the degree of muscle trauma or injury (8).
Hepatocyte Growth Factor
HGF is a cytokine with various different cellular functions. Specific to skeletal muscle hypertrophy, HGF activates satellite cells and may be responsible for causing satellite cells to migrate to the injured area (2).
Hormones in Skeletal Muscle Hypertrophy
Hormones are chemicals which organs secrete to initiate or regulate the activity of an organ or group of cells in another part of the body. It should be noted that hormone function is decidedly affected by nutritional status, foodstuff intake and lifestyle factors such as stress, sleep, and general health. The following hormones are of special interest in skeletal muscle hypertrophy.
Growth hormone (GH) is a peptide hormone that stimulates IGF in skeletal muscle, promoting satellite cell activation, proliferation and differentiation (9). However, the observed hypertrophic effects from the additional administration of GH, investigated in GH-treated groups doing resistance exercise, may be less credited with contractile protein increase and more attributable to fluid retention and accumulation of connective tissue (9).
Cortisol is a steroid hormone (hormones which have a steroid nucleus that can pass through a cell membrane without a receptor) which is produced in the adrenal cortex of the kidney. It is a stress hormone, which stimulates gluconeogenesis, which is the formation of glucose from sources other than glucose, such as amino acids and free fatty acids. Cortisol also inhibits the use of glucose by most body cells. This can initiate protein catabolism (break down), thus freeing amino acids to be used to make different proteins, which may be necessary and critical in times of stress.
In terms of hypertrophy, an increase in cortisol is related to an increased rate of protein catabolism. Therefore, cortisol breaks down muscle proteins, inhibiting skeletal muscle hypertrophy (10).
Testosterone is an androgen, or a male sex hormone. The primary physiological role of androgens are to promote the growth and development of male organs and characteristics. Testosterone affects the nervous system, skeletal muscle, bone marrow, skin, hair and the sex organs.
With skeletal muscle, testosterone, which is produced in significantly greater amounts in males, has an anabolic (muscle building) effect. This contributes to the gender differences observed in body weight and composition between men and women. Testosterone increases protein synthesis, which induces hypertrophy (11).
Fiber Types and Skeletal Muscle Hypertrophy
The force generated by a muscle is dependent on its size and the muscle fiber type composition. Skeletal muscle fibers are classified into two major categories; slow-twitch (Type 1) and fast-twitch fibers (Type II). The difference between the two fibers can be distinguished by metabolism, contractile velocity, neuromuscular differences, glycogen stores, capillary density of the muscle, and the actual response to hypertrophy (12).
Type I Fibers
Type I fibers, also known as slow twitch oxidative muscle fibers, are primaritly responsible for maintenance of body posture and skeletal support. The soleus is an example of a predominantly slow-twitch muscle fiber. An increase in capillary density is related to Type I fibers because they are more involved in endurance activities. These fibers are able to generate tension for longer periods of time. Type I fibers require less excitation to cause a contraction, but also generate less force. They utilize fats and carbohydrates better because of the increased reliance on oxidative metabolism (the body’s complex energy system that transforms energy from the breakdown of fuels with the assistance of oxygen) (12).
Type I fibers have been shown to hypertrophy considerably due to progressive overload (13,15). It is interesting to note that there is an increase in Type I fiber area not only with resistance exercise, but also to some degree with aerobic exercise (14).
Type II Fibers
Type II fibers can be found in muscles which require greater amounts of force production for shorter periods of time, such as the gastrocnemius and vastus lateralis. Type II fibers can be further classified as Type IIa and Type IIb muscle fibers.
Type IIa Fibers
Type IIa fibers, also known as fast twitch oxidative glycolytic fibers (FOG), are hybrids between Type I and IIb fibers. Type IIa fibers carry characteristics of both Type I and IIb fibers. They rely on both anaerobic (reactions which produce energy that do not require oxygen), and oxidative metabolism to support contraction (12).
With resistance training as well as endurance training, Type IIb fibers convert into Type IIa fibers, causing an increase in the percentage of Type IIa fibers within a muscle (13). Type IIa fibers also have an increase in cross sectional area resulting in hypertrophy with resistance exercise (13). With disuse and atrophy, the Type IIa fibers convert back to Type IIb fibers.
Type IIb Fibers
Type IIb fibers are fast-twitch glycolytic fibers (FG). These fibers rely solely on anaerobic metabolism for energy for contraction, which is the reason they have high amounts of glycolytic enzymes. These fibers generate the greatest amount of force due to an increase in the size of the nerve body, axon and muscle fiber, a higher conduction velocity of alpha motor nerves, and a higher amount of excitement necessary to start an action potential (12). Although this fiber type is able to generate the greatest amount of force, it is also maintains tension for a shortesst period of time (of all the muscle fiber types).
Type IIb fibers convert into Type IIa fibers with resistance exercise. It is believed that resistance training causes an increase in the oxidative capacity of the strength-trained muscle. Because Type IIa fibers have a greater oxidative capacity than Type IIb fibers, the change is a positive adaptation to the demands of exercise (13).
Muscular hypertrophy is a multidimensional process, with numerous factors involved. It involves a complex interaction of satellite cells, the immune system, growth factors, and hormones with the individual muscle fibers of each muscle. Although our goals as fitness professionals and personal trainers motivates us to learn new and more effective ways of training the human body, the basic understanding of how a muscle fiber adapts to an acute and chronic training stimulus is an important educational foundation of our profession.
Table 1. Structural Changes that Occur as a Result of Muscle Fiber Hypertrophy
Increase in actin filaments
Increase in myosin filaments
Increase in myofibrils
Increase in sarcoplasm
Increase in muscle fiber connective tissue
Source: Wilmore, J.H. and D. L. Costill. Physiology of Sport and Exercise (2nd Edition).Champaign, IL: Human Kinetics, 1999.
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