scholarly journals Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type

2010 ◽  
Vol 109 (3) ◽  
pp. 635-642 ◽  
Author(s):  
Samuel M. Cadena ◽  
Kathleen N. Tomkinson ◽  
Travis E. Monnell ◽  
Matthew S. Spaits ◽  
Ravindra Kumar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Musculoskeletal Diseases ◽  
Fiber Type ◽  
Cross Sectional Area ◽  
Soluble Form ◽  
Control Group ◽  
Type I ◽  
Type Ii ◽  
Sectional Area ◽  
Cross Sectional

This is the first report that inhibition of negative regulators of skeletal muscle by a soluble form of activin type IIB receptor (ACE-031) increases muscle mass independent of fiber-type expression. This finding is distinct from the effects of selective pharmacological inhibition of myostatin (GDF-8), which predominantly targets type II fibers. In our study 8-wk-old C57BL/6 mice were treated with ACE-031 or vehicle control for 28 days. By the end of treatment, mean body weight of the ACE-031 group was 16% greater than that of the control group, and wet weights of soleus, plantaris, gastrocnemius, and extensor digitorum longus muscles increased by 33, 44, 46 and 26%, respectively ( P < 0.05). Soleus fiber-type distribution was unchanged with ACE-031 administration, and mean fiber cross-sectional area increased by 22 and 28% ( P < 0.05) in type I and II fibers, respectively. In the plantaris, a predominantly type II fiber muscle, mean fiber cross-sectional area increased by 57% with ACE-031 treatment. Analysis of myosin heavy chain (MHC) isoform transcripts by real-time PCR indicated no change in transcript levels in the soleus, but a decline in MHC I and IIa in the plantaris. In contrast, electrophoretic separation of total soleus and plantaris protein indicated that there was no change in the proportion of MHC isoforms in either muscle. Thus these data provide optimism that ACE-031 may be a viable therapeutic in the treatment of musculoskeletal diseases. Future studies should be undertaken to confirm that the observed effects are not age dependent or due to the relatively short study duration.

The Effects of Non-Weight Bearing on Skeletal Muscle in Older Rats: an Interrupted Bout versus an Uninterrupted Bout

2004 ◽  
Vol 5 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Alissa Guildner Gehrke ◽  
Margaret Sheie Krull ◽  
Robin Shotwell McDonald ◽  
Tracy Sparby ◽  
Jessica Thoele ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Weight Bearing ◽  
Cross Sectional Area ◽  
Type I ◽  
Type Ii ◽  
Sectional Area ◽  
Cross Sectional ◽  
Age Related ◽  
Type Ii Fibers

Age-related changes in skeletal muscle, in combination with bed rest, may result in a poorer rehabilitation potential for an elderly patient. The purpose of this study was to determine the effects of non-weight bearing (hind limb unweighting [HU]) on the soleus and extensor digitorum longus (EDL) in older rats. Two non-weight bearing conditions were used: an uninterrupted bout of HU and an interrupted bout of HU. Twenty-one rats were randomly placed into 1 of 3 groups: control, interrupted HU (2 phases of 7 days of HU, separated by a 4-day weight-bearing phase) and an uninterrupted HU (18 uninterrupted days of HU). Following non-weight bearing, the soleus and EDL muscles were removed. Fiber type identification was performed by myofibrillar ATPase and cross-sectional area was determined. The findings suggest that any period of non-weight bearing leads to a decrease in muscle wet weight (19%-45%). Both type I and type II fibers of the soleus showed atrophy (decrease in cross-sectional area, 35%-44%) with an uninterrupted bout of non-weight bearing. Only the type II fibers of the soleus showed recovery with an interrupted bout of weight bearing. In the EDL, type II fibers were more affected by an uninterrupted bout of non-weight bearing (15% decrease in fiber size) compared to the type I fibers. EDL type II fibers showed more atrophy with interrupted bouts of non-weight bearing than with a single bout (a 40% compared to a 15% decrease). This study shows that initial weight bearing after an episode of non-weight bearing may be damaging to type II fibers of the EDL.

Diaphragm capillarity and oxidative capacity during postnatal development

1991 ◽  
Vol 70 (1) ◽  
pp. 103-111 ◽  
Author(s):  
G. C. Sieck ◽  
T. S. Cheung ◽  
C. E. Blanco
Keyword(s):  
Postnatal Development ◽  
Fiber Type ◽  
Processing System ◽  
Oxidative Capacity ◽  
Cross Sectional Area ◽  
Type I ◽  
Type Ii ◽  
Sectional Area ◽  
Cross Sectional ◽  
Type Ii Fibers

In the cat diaphragm, fiber capillarity, cross-sectional area, and succinate dehydrogenase (SDH) activity were measured across the first 6 wk of postnatal development. Fibers were classified as type I, IIa, IIb, or IIc on the basis of staining for myofibrillar adenosinetriphosphatase (ATPase). Capillaries were identified in sections stained for ATPase at pH 4.2. Fiber cross-sectional areas and SDH activities were quantified using an image-processing system. During postnatal development, the proportions of type I fibers increased while type II fibers decreased. At birth, all type II fibers were IIc. From the 1st to the 2nd postnatal wk, the proportion of type IIc fibers decreased while the numbers of IIa and IIb increased. Thereafter the proportion of type IIb fibers continued to increase while the number of IIa steadily declined. At birth, capillarity, cross-sectional areas, and SDH activities of type I and II fibers were low compared with other postnatal age groups. Fiber cross-sectional areas increased progressively with age. The number of capillaries surrounding type I and II fibers increased markedly by the 2nd wk and then continued to increase at a slower rate. The number of capillaries per fiber area reached a peak by the 2nd wk and then declined as fiber cross-sectional area increased. Postnatal changes in capillarity depended on fiber type, being greatest in IIb. SDH activities of type I and II fibers were initially low during the first 2 postnatal wk and then peaked by the 3rd wk. After the 6th wk, fiber SDH activities decreased to adult values. Among the type II fibers, IIb showed the greatest change in SDH activity during early postnatal development.

Interactive effects of emphysema and malnutrition on diaphragm structure and function

1994 ◽  
Vol 77 (2) ◽  
pp. 947-955 ◽  
Author(s):  
M. I. Lewis ◽  
S. A. Monn ◽  
W. Z. Zhan ◽  
G. C. Sieck
Keyword(s):  
Succinate Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Cross Sectional Area ◽  
Interactive Effects ◽  
Type I ◽  
Specific Force ◽  
Type Ii ◽  
Sectional Area ◽  
Succinate Dehydrogenase Activity ◽  
Cross Sectional

Interactive effects of emphysema (EMP) and prolonged nutritional deprivation (ND) on contractile, morphometric, and metabolic properties of hamster diaphragm muscle (DIA) were examined. Six months after induction of EMP (intratracheal elastase), saline-treated controls (CTL) and EMP hamsters of similar body weights were subjected to ND over 6 wk. Isometric contractile and fatigue properties of costal DIA were determined in vitro. DIA fibers were histochemically classified as type I or II, and fiber succinate dehydrogenase activity and cross-sectional area were determined using quantitative microscopic procedures. From histochemical sections, the number of capillaries per fiber (C/F) and per fiber cross-sectional area (C/A) were determined. ND resulted in progressive loss of body weight (ND-CTL, 23.8%; ND-EMP, 28.4%; P = NS). ND did not affect reduction in optimal length (Lo) of DIA fibers in EMP compared with CTL and ND-CTL hamsters. Maximum specific force (i.e., force/unit area) was reduced by approximately 25% in EMP animals compared with CTL. ND did not improve or exacerbate the reduction in specific force with EMP. ND attenuated improved fatigue resistance of DIA in EMP animals. No differences in fiber type proportions were noted among experimental groups. Significant atrophy of type I and II DIA fibers was noted after ND. Atrophy was proportionately greater in type II fibers of ND-EMP when referenced to EMP animals. Thus adaptive hypertrophy of type II DIA fibers in EMP animals was abolished. Fiber succinate dehydrogenase activity was significantly increased in type I and II fibers in EMP DIA. ND did not affect this metabolic adaptation of DIA fibers to persistent loads imposed by EMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of starvation and refeeding on adult male rat diaphragm contractility, fatigue, and fiber types

1993 ◽  
Vol 74 (2) ◽  
pp. 742-749 ◽  
Author(s):  
D. J. Prezant ◽  
D. E. Valentine ◽  
H. H. Kim ◽  
E. I. Gentry
Keyword(s):  
Fatigue Resistance ◽  
Cross Sectional Area ◽  
Male Rats ◽  
Male Rat ◽  
Type I ◽  
Fiber Types ◽  
Type Ii ◽  
Sectional Area ◽  
Cross Sectional ◽  
Type Ii Fibers

The effects of 4.5 days of acute starvation, either alone or followed by refeeding (ad libitum), on diaphragm contractility, fatigue, and fiber types were studied in male rats. Contractility and fatigue resistance indexes were measured in an in vitro costal diaphragm strip preparation with direct stimulation at 37 degrees C. Compared with controls, starvation produced a 28 +/- 1% (P < 0.001) reduction in body weight and an 18 +/- 4% (P < 0.001) reduction in costal diaphragm weight. Twitch and tetanic tensions (normalized for weight or cross-sectional area) were not reduced by starvation. Starvation produced significant increases in fatigue resistance indexes after a 5-Hz stimulation paradigm but not after a 100-Hz paradigm, supporting the hypothesis that fatigue resistance is dependent on the energy demand of a given paradigm. The proportions of type I and type II fibers were similar between diaphragms of starved and control rats, but the cross-sectional area of type II fibers decreased significantly by 18 +/- 7% (P < 0.01). Thus, despite the significant decrease in diaphragm weight after starvation, contractility was preserved and fatigue resistance was increased (low-output paradigm). This is consistent with the decrease in type II fiber area. Refeeding restored all parameters so that there were no longer significant differences in body or diaphragm weight, contractility, fatigue, or fiber types.

Strength, skeletal muscle composition, and enzyme activity in multiple sclerosis

1997 ◽  
Vol 83 (6) ◽  
pp. 1998-2004 ◽  
Author(s):  
J. A. Kent-Braun ◽  
A. V. Ng ◽  
M. Castro ◽  
M. W. Weiner ◽  
D. Gelinas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Skeletal Muscle ◽  
Enzyme Activity ◽  
Succinic Dehydrogenase ◽  
Morphological Characteristics ◽  
Cross Sectional Area ◽  
Type I ◽  
Sectional Area ◽  
Cross Sectional ◽  
Muscle Composition

Kent-Braun, J. A., A. V. Ng, M. Castro, M. W. Weiner, D. Gelinas, G. A. Dudley, and R. G. Miller. Strength, skeletal muscle composition and enzyme activity in multiple sclerosis. J. Appl. Physiol. 83(6): 1998–2004, 1997.—This study examined functional, biochemical, and morphological characteristics of skeletal muscle in nine multiple sclerosis (MS) patients and eight healthy controls in an effort to ascertain whether intramuscular adaptations could account for excessive fatigue in this disease. Analyses of biopsies of the tibialis anterior muscle showed that there were fewer type I fibers (66 ± 6 vs. 76 ± 6%), and that fibers of all types were smaller (average ↓26%) and had lower succinic dehydrogenase (SDH; average ↓40%) and SDH/α-glycerol-phosphate dehydrogenase (GPDH) but not GPDH activities in MS vs. control subjects, suggesting that muscle in this disease is smaller and relies more on anaerobic than aerobic-oxidative energy supply than does muscle of healthy individuals. Maximal voluntary isometric force for dorsiflexion was associated with both average fiber cross-sectional area ( r = 0.71, P = 0.005) and muscle fat-free cross-sectional area by magnetic resonance imaging ( r = 0.80, P < 0.001). Physical activity, assessed by accelerometer, was associated with average fiber SDH/GPDH ( r = 0.78, P = 0.008). There was a tendency for symptomatic fatigue to be inversely associated with average fiber SDH activity ( r = −0.57, P = 0.068). The results of this study suggest that the inherent characteristics of skeletal muscle fibers per se and of skeletal muscle as a whole are altered in the direction of disuse in MS. They also suggest that changes in skeletal muscle in MS may significantly affect function.

Aging, muscle fiber type, and contractile function in sprint-trained athletes

2006 ◽  
Vol 101 (3) ◽  
pp. 906-917 ◽  
Author(s):  
Marko T. Korhonen ◽  
Alexander Cristea ◽  
Markku Alén ◽  
Keijo Häkkinen ◽  
Sarianna Sipilä ◽  
...  
Keyword(s):  
Fiber Type ◽  
Cross Sectional Area ◽  
Rate Of Force Development ◽  
Knee Extensors ◽  
Type I ◽  
Sectional Area ◽  
Cross Sectional ◽  
Specific Tension ◽  
Force Development ◽  
Aging Muscle

Biopsy samples were taken from the vastus lateralis of 18- to 84-yr-old male sprinters ( n = 91). Fiber-type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content were identified using ATPase histochemistry and SDS-PAGE. Specific tension and maximum shortening velocity ( Vo) were determined in 144 single skinned fibers from younger (18–33 yr, n = 8) and older (53–77 yr, n = 9) runners. Force-time characteristics of the knee extensors were determined by using isometric contraction. The cross-sectional area of type I fibers was unchanged with age, whereas that of type II fibers was reduced ( P < 0.001). With age there was an increased MHC I ( P < 0.01) and reduced MHC IIx isoform content ( P < 0.05) but no differences in MHC IIa. Specific tension of type I and IIa MHC fibers did not differ between younger and older subjects. Vo of fibers expressing type I MHC was lower ( P < 0.05) in older than in younger subjects, but there was no difference in Vo of type IIa MHC fibers. An aging-related decline of maximal isometric force ( P < 0.001) and normalized rate of force development ( P < 0.05) of knee extensors was observed. Normalized rate of force development was positively associated with MHC II ( P < 0.05). The sprint-trained athletes experienced the typical aging-related reduction in the size of fast fibers, a shift toward a slower MHC isoform profile, and a lower Vo of type I MHC fibers, which played a role in the decline in explosive force production. However, the muscle characteristics were preserved at a high level in the oldest runners, underlining the favorable impact of sprint exercise on aging muscle.

scholarly journals Automated fiber-type-specific cross-sectional area assessment and myonuclei counting in skeletal muscle

2013 ◽  
Vol 115 (11) ◽  
pp. 1714-1724 ◽  
Author(s):  
Fujun Liu ◽  
Christopher S. Fry ◽  
Jyothi Mula ◽  
Janna R. Jackson ◽  
Jonah D. Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Cross Sectional Area ◽  
Automated Image Analysis ◽  
Muscle Fiber Type ◽  
Sectional Area ◽  
Cross Sectional ◽  
Exercise Interventions ◽  
Structural And Functional Properties

Skeletal muscle is an exceptionally adaptive tissue that compromises 40% of mammalian body mass. Skeletal muscle functions in locomotion, but also plays important roles in thermogenesis and metabolic homeostasis. Thus characterizing the structural and functional properties of skeletal muscle is important in many facets of biomedical research, ranging from myopathies to rehabilitation sciences to exercise interventions aimed at improving quality of life in the face of chronic disease and aging. In this paper, we focus on automated quantification of three important morphological features of muscle: 1) muscle fiber-type composition; 2) muscle fiber-type-specific cross-sectional area, and 3) myonuclear content and location. We experimentally prove that the proposed automated image analysis approaches for fiber-type-specific assessments and automated myonuclei counting are fast, accurate, and reliable.

Statistical Analysis of Fiber Area in Human Skeletal Muscle

2002 ◽  
Vol 27 (4) ◽  
pp. 415-422 ◽  
Author(s):  
Michael R.M. Mcguigan ◽  
William J. Kraemer ◽  
Michael R. Deschenes ◽  
Scott E. Gordon ◽  
Takashi Kitaura ◽  
...  
Keyword(s):  
Fiber Type ◽  
Cross Sectional Area ◽  
Type I ◽  
Fiber Types ◽  
Sectional Area ◽  
Cross Sectional ◽  
Fiber Area ◽  
Random Block ◽  
Type I Fibers ◽  
Accurate Reflection

Previous research has indicated that 50 fiber measurements per individual for type I and II fibers would be sufficient to characterize the fiber areas. This study replicated the work of McCall et al. (1998) using the three major fiber types (I, IIA, and IIB) and sampling larger populations of fibers. Random blocks of fibers were also examined to investigate how well they correlated with the overall mean average fiber area. Using random blocks of 50 fibers provided an accurate reflection of the type IIB fibers (r = 0.96-0.98) but not for the type I (r = 0.85-0.94) or IIA fibers (r = 0.80-0.91). Type I fibers were consistently reflected by a random block of 150 fibers (r = 0.95-0.98) while type IIA fibers required random blocks of 200 fibers (r = 0.94-0.98), which appeared to provide an accurate reflection of the cross-sectional area. These results indicate that for a needle biopsy different numbers of fibers are needed depending on the fiber type to accurately characterize the mean fiber population. Key words: fiber type, sample size, cross-sectional area, biopsy

Modulation of myonuclear number in functionally overloaded and exercised rat plantaris fibers

1999 ◽  
Vol 87 (2) ◽  
pp. 634-642 ◽  
Author(s):  
Roland R. Roy ◽  
Steven R. Monke ◽  
David L. Allen ◽  
V. Reggie Edgerton
Keyword(s):  
Fiber Type ◽  
Domain Size ◽  
Cross Sectional Area ◽  
Type I ◽  
Fiber Types ◽  
Sectional Area ◽  
Tight Coupling ◽  
Fiber Volume ◽  
Cross Sectional ◽  
Myonuclear Domain

The effects of 10 wk of functional overload (FO), with and without daily treadmill endurance training, on the cross-sectional area, myonuclear number, and myonuclear domain size of mechanically isolated single fiber segments of the adult rat plantaris were determined. The fibers were typed on the basis of high-resolution gel electrophoresis for separation of specific myosin heavy chain (MHC) isoforms and grouped as type I+ (containing some type I MHC with or without any combination of fast MHCs), type IIa+ (containing some type IIa with or without some type IIx and/or IIb but no type I MHC), and type IIx/b (containing only type IIx and/or IIb MHCs). Type I+ fibers had a higher myonuclear number than did both fast types of fibers in the control and FO, but not in the FO and treadmill trained, rats. All fiber types in both FO groups had a significantly larger (36–90%) cross-sectional area and a significantly higher (61–109%) myonuclear number than did control. The average myonuclear domain size of each fiber type was similar among the three groups, except for a smaller domain size in the type IIx/b fibers of the FO compared with control. In general, these data indicate that during hypertrophy the number of myonuclei increase proportionally to the increase in fiber volume. The maintenance of myonuclear domain size near control values suggests that regulatory mechanisms exist that ensure a tight coupling between the quantity of genetic machinery and the protein requirements of a fiber.

scholarly journals Denervation effects on myonuclear domain size of rat diaphragm fibers

2006 ◽  
Vol 100 (5) ◽  
pp. 1617-1622 ◽  
Author(s):  
Bharathi Aravamudan ◽  
Carlos B. Mantilla ◽  
Wen-Zhi Zhan ◽  
Gary C. Sieck
Keyword(s):  
Fiber Type ◽  
Cross Sectional Area ◽  
Diaphragm Muscle ◽  
Type I ◽  
Fiber Types ◽  
Sectional Area ◽  
Rat Diaphragm ◽  
Cross Sectional ◽  
Fiber Size ◽  
Myonuclear Domain

Denervation (DNV) of rat diaphragm muscle (DIAm) leads to selective atrophy of type IIx and IIb fibers, whereas the cross-sectional area of type I and IIa fibers remains unchanged or slightly hypertrophied. DIAm DNV also increases satellite cell mitotic activity and myonuclear apoptosis. Similar to other skeletal muscles, DIAm fibers are multinucleated, and each myonucleus regulates the gene products in a finite fiber volume, i.e., myonuclear domain (MND). MND size varies across DIAm fiber types in rank order, I < IIa < IIx < IIb [fiber type based on myosin heavy chain isoform expression]. We hypothesized that, after DNV, the total number of myonuclei per fiber does not change and, accordingly, that MND changes proportionately to the change in fiber size regardless of fiber type. Adult rats underwent unilateral (right side) DIAm DNV, and after 2 wk single fibers were dissected. Fiber cross-sectional area, myonuclear number, and MND were measured by confocal microscopy, and these values in DNV DIAm were compared with those obtained in controls. After DNV, type I fibers hypertrophied, type IIa fiber size was unchanged, and type IIx and IIb fibers atrophied compared with control. The total number of myonuclei per fiber was not affected by DNV. Accordingly, after DNV, type I fiber MND increased by 25%, whereas it decreased in type IIx and IIb fibers by 50 and 70%, respectively. These results suggest that MND is not maintained after DNV-induced DIAm fiber hypertrophy or atrophy. These results are interpreted with respect to consequent effects of DNV on myonuclear transcriptional activity and protein turnover.

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