Muscle Fiber Hypertrophy vs. Hyperplasia

[O-Train]

A lot of the studies are quite old (both for and against) this one is relatively new.

Skeletal muscle morphology and exercise response in congenital generalized lipodystrophy.
Garg A, Stray-Gundersen J, Parsons D, Bertocci LA.

Department of Internal Medicine, The Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas 75390-9052, USA. agarg@mednet.swmed.edu

OBJECTIVE: Congenital generalized lipodystrophy (CGL) is an autosomal recessive genetic disorder characterized by almost complete absence of adipose tissue, muscular appearance, and severe insulin resistance since birth. We investigated whether insulin resistance in CGL patients is associated with abnormal muscle morphology and whether increased muscularity imparts increased muscle strength and exercise capacity RESEARCH DESIGN AND METHODS: We obtained quadriceps muscle biopsies to study muscle fiber types and capillary density in three African-American women (aged 17-20 years) with CGL. We also assessed quadriceps muscle strength, muscle metabolism, and maximal O2 consumption in the patients. RESULTS: Quadriceps muscle biopsies revealed a markedly higher percentage of type II (fast-twitch glycolytic) muscle fibers in patients with CGL versus sedentary young women (75-78 vs. 47-57%, respectively). The capillary-to-fiber ratio (2.7-3.0), however, was normal. Cross-sectional areas of type I (slow-twitch oxidative) (1,262-2,685 microm2) and type II (2,304-3,594 microm2) fibers were far below the normal values (3,811-4,310 and 3,115-4,193 microm2, respectively), suggesting muscle hyperplasia but not hypertrophy The quadriceps muscle strength, as measured by Cybex, was below average; the maximal O2 consumption (23-32 ml x kg(-1) x min(-1)) was also below average. 31P nuclear magnetic resonance spectroscopy of the forearm muscles revealed normal pH and metabolic responses to static and dynamic exercises. CONCLUSIONS: We conclude that insulin resistance in patients with CGL is associated with an increased proportion of type II muscle fibers but not reduced capillary density. Increased muscularity in CGL is due to muscle hyperplasia and is not associated with increased muscle strength.

Link to free full text: http://www.ncbi.nlm.nih.gov/pubmed/1...&ordinalpos=18

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If you had read my initial post you would know that they have also looked at other animal models. It's very difficult to determine if hyperplasia is occuring in humans and even the author that promotes hyperplasia admits that only certain stimulus and conditions ilicit the response.

Note the term - meta-analysis this is a reading of other studies. Neither of the two studies quoted actually did research.
There is evidence of muscular hyperplasia in birds.
There is not in humans.

[tiramisu]

this one is interesting.... reading the study now.

[O-Train]

A meta-analysis is much more scientifically valid than a singular study. Just like a peer reviewed article is more likely to be accurate than one that is not peer reviewed.

[tiramisu]

The last study seems to be pointing down the IGF route to hyperplasia. This is the one that I would LIKE to believe has some merit. This is interesting. The authors pretty much admit to not understanding mechanism or event but the observations are very interesting. The subjects are serious freaks of nature.

[tiramisu]

A meta-analysis is much more scientifically valid than a singular study. Just like a peer reviewed article is more likely to be accurate than one that is not peer reviewed.

Yes but when you take a look at the bibliography it's almost entirely avian studies.

[O-Train]

The last study seems to be pointing down the IGF route to hyperplasia. This is the one that I would LIKE to believe has some merit. This is interesting. The authors pretty much admit to not understanding mechanism or event but the observations are very interesting. The subjects are serious freaks of nature.

I've read some other stuff regarding IGF too. Like this study for example:
http://www.ncbi.nlm.nih.gov/pubmed/1...&ordinalpos=15

Chicken embryos though. Good studies done on humans are few and far between. Too many ethical bridges to cross.

This is also kind of an interesting study done on rats.

New fiber formation in the interstitial spaces of rat skeletal muscle during postnatal growth.
Tamaki T, Akatsuka A, Yoshimura S, Roy RR, Edgerton VR.

Department of Physiology, Division of Human Structure and Function, Tokai University University School of Medicine, Kanagawa, Japan. tamaki@is.icc.u-tokai.ac.jp

The purpose of this study was to determine whether fiber hyperplasia occurs in the rat plantaris muscle during postnatal weeks 3-20. Total muscle fiber number, obtained via the nitric acid digestion method, increased by 28% during the early postnatal rapid growth phase (3-10 weeks), whereas the number of branched fibers was consistently low. Whole-muscle mitotic activity and amino acid uptake levels showed an inverse relationship to the increase in total fiber number. The expression of MyoD mRNA (RT-PCR) levels decreased from 3 to 20 weeks of age, as did the detection of anti-BrdU- and MyoD-positive cells in histological sections. Immunohistochemical staining patterns for MyoD, myogenin, or developmental myosin heavy chain on sections stained for laminin (identification of the basal lamina) and electron micrographs clearly indicate that de novo fiber formation occurred in the interstitial spaces. Myogenic cells in the interstitial spaces were negative for the reliable specific satellite cell marker M-cadherin. In contrast, CD34 (an established marker for hematopoietic stem cells)-positive cells were located only in the interstitial spaces, and their frequency and location were similar to those of MyoD- and/or myogenin-positive cells. These findings are consistent with fiber hyperplasia occurring in the interstitial spaces of the rat plantaris muscle during the rapid postnatal growth phase. Furthermore, these data suggest that the new fibers may be formed from myogenic cells in the interstitial spaces of skeletal muscle and may express CD34 that is distinct from satellite cells.

[O-Train]

The subjects are serious freaks of nature.

So is this lady! Can't get the full text but I'm really curious what she looks like:

Congenital monomelic muscular hypertrophy of the upper extremity.
Gilhuis HJ, Zöphel OT, Lammens M, Zwarts MJ.

Department of Neurology, Reinier de Graaf Hospital, P.O. Box 5011, Delft 2600 GA, The Netherlands. gilhuis@rdgg.nl

Pathological muscular hypertrophy results from either muscular or neurogenic damage. Rarely, it is caused by a congenital malformation consisting of a unilateral muscular hyperplasia of the upper extremity. We report on a young woman with an enlargement of the right upper extremity. Electromyography showed polyphasic, large motor unit potentials in the affected muscles. MRI and ultrasound assessment demonstrated diffuse enlargement of muscle mass without signs of edema. Muscle biopsy revealed sections with marked variations in fiber size with no signs of inflammation or marked loss of muscle fibers. Factors assumed to be important in the pathophysiology of this phenomenon are discussed.

[O-Train]

I'm starting to think that maybe myostatin has a role in this also. Not sure how or why though.

Prolonged absence of myostatin reduces sarcopenia.
Siriett V, Platt L, Salerno MS, Ling N, Kambadur R, Sharma M.

Functional Muscle Genomics, AgResearch, East Street, Hamilton, New Zealand.

Sarcopenia is a progressive age-related loss of skeletal muscle mass and strength. Parabiotic experiments show that circulating factors positively influence the proliferation and regenerative capacity of satellite cells in aged mice. In addition, we believe that negative regulators of muscle mass also serve to balance the signals that influence satellite cell activation and regeneration capacity with ageing. Myostatin, a negative regulator of pre- and postnatal myogenesis, inhibits satellite cell activation and muscle regeneration postnatally. To investigate the role of myostatin during age-related sarcopenia, we examined muscle mass and regeneration in young and old myostatin-null mice. Young myostatin-null muscle fibers were characterized by massive hypertrophy and hyperplasia and an increase in type IIB fibers, resulting in a more glycolytic muscle. With ageing, wild-type muscle became increasingly oxidative and fiber atrophy was prominent. In contrast no fiber type switching was observed and atrophy was minimal in aged myostatin-null muscle. The effect of ageing on satellite cell numbers appeared minimal, however, satellite cell activation declined significantly in both wild-type and myostatin-null muscles. In young mice, lack of myostatin resulted in increased satellite cell number and activation compared to wild-type, suggesting a greater propensity to undergo myogenesis, a difference maintained in the aged mice. In addition, muscle regeneration of myostatin-null muscle following notexin injury was accelerated and fiber hypertrophy and type were recovered with regeneration, unlike in wild-type muscle. In conclusion, a lack of myostatin appears to reduce age-related sarcopenia and loss of muscle regenerative capacity. (c) 2006 Wiley-Liss, Inc.

[O-Train]

It won't be long before fat people go to their doctor for a myostatin blocking shot. Getting way off topic but I find this stuff interesting.

Suppression of body fat accumulation in myostatin-deficient mice.
McPherron AC, Lee SJ.

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Myostatin is a TGF-beta family member that acts as a negative regulator of muscle growth. Mice lacking the myostatin gene (Mstn) have a widespread increase in skeletal muscle mass resulting from a combination of muscle fiber hypertrophy and hyperplasia. Here we show that Mstn-null mice have a significant reduction in fat accumulation with increasing age compared with wild-type littermates, even in the setting of normal food intake (relative to body weight), normal body temperature, and a slightly decreased resting metabolic rate. To investigate whether myostatin might be an effective target for suppressing the development of obesity in settings of abnormal fat accumulation, we analyzed the effect of the Mstn mutation in two genetic models of obesity, agouti lethal yellow (A(y)) and obese (Lep(ob/ob)). In each case, loss of Mstn led to a partial suppression of fat accumulation and of abnormal glucose metabolism. Our findings raise the possibility that pharmacological agents that block myostatin function may be useful not only for enhancing muscle growth, but also for slowing or preventing the development of obesity and type 2 diabetes.