Early accentuated muscle hypertrophy is strongly associated with myonuclear accretion

2020 ◽  
Vol 319 (1) ◽  
pp. R50-R58
Author(s):  
Tommy R. Lundberg ◽  
Luis Manuel Martínez-Aranda ◽  
Gema Sanz ◽  
Björn Hansson ◽  
Ferdinand von Walden ◽  
...  

The current study explored whether the marked hypertrophic response noted with a short-term unilateral concurrent exercise paradigm was associated with more prominent changes in myonuclei accretion, ribosome biogenesis, and capillarization compared with resistance exercise alone (RE). Ten men (age 25 ± 4 yr) performed aerobic and resistance exercise (AE + RE) for one leg while the other leg did RE. Muscle biopsies were obtained before and after 5 wk of training and subjected to fiber-type specific immunohistochemical analysis, and quantification of total RNA content and mRNA/rRNA transcript abundance. Type II fiber cross-sectional area (CSA) increased with both AE + RE (22%) and RE (16%), while type I fiber CSA increased mainly with AE + RE (16%). The change score tended to differ between legs for type I CSA ( P = 0.099), and the increase in smallest fiber diameter was greater in AE + RE than RE ( P = 0.029). The number of nuclei per fiber increased after AE + RE in both fiber types, and this increase was greater ( P = 0.027) than after RE. A strong correlation was observed between changes in number of nuclei per fiber and fiber CSA in both fiber types, for both AE + RE and RE ( r > 0.8, P < 0.004). RNA content increased after AE + RE (24%, P = 0.019), but the change-scores did not differ across legs. The capillary variables generally increased in both fiber types, with no difference across legs. In conclusion, the accentuated hypertrophic response to AE + RE was associated with more pronounced myonuclear accretion, which was strongly correlated with the degree of fiber hypertrophy. This suggests that myonuclear accretion could play a role in facilitating muscle hypertrophy also during very short training periods.

1991 ◽  
Vol 71 (2) ◽  
pp. 558-564 ◽  
Author(s):  
P. F. Gardiner ◽  
B. J. Jasmin ◽  
P. Corriveau

Our aim was to quantify the overload-induced hypertrophy and conversion of fiber types (type II to I) occurring in the medial head of the gastrocnemius muscle (MG). Overload of MG was induced by a bilateral tenotomy/retraction of synergists, followed by 12–18 wk of regular treadmill locomotion (2 h of walking/running per day on 3 of 4 days). We counted all type I fibers and determined type I and II mean fiber areas in eight equidistant sections taken along the length of control and overloaded MG. Increase in muscle weights (31%), as well as in total muscle cross-sectional areas (37%) and fiber areas (type I, 57%; type II, 34%), attested to a significant hypertrophic response in overloaded MG. An increase in type I fiber composition of MG from 7.0 to 11.5% occurred as a result of overload, with the greatest and only statistically significant changes (approximately 70–100%) being found in sections taken from the most rostral 45% of the muscle length. Results of analysis of sections taken from the largest muscle girth showed that it significantly underestimated the extent of fiber conversion that occurred throughout the muscle as a whole. These data obtained on the MG, which possesses a compartmentalization of fiber types, support the notion that all fiber types respond to this model with a similar degree of hypertrophy. Also, they emphasize the complex nature of the adaptive changes that occur in these types of muscles as a result of overload.


1992 ◽  
Vol 263 (5) ◽  
pp. R1093-R1098 ◽  
Author(s):  
S. K. Powers ◽  
D. Criswell ◽  
F. K. Lieu ◽  
S. Dodd ◽  
H. Silverman

Limited data exist concerning the effects of exercise training on cellular oxidative capacity in the diaphragm of senescent animals. In this study we examined the changes in cellular oxidative capacity, muscle cell cross-sectional area (CSA), and capillarity within the costal diaphragm of senescent animals after a 10-wk endurance-training program. Twelve 24-mo-old female Fischer 344 rats were divided into either a sedentary control group (n = 6) or exercise training group (n = 6). The trained animals exercised on a motor-driven treadmill (60 min/day, 5 days/wk) at a work rate equal to approximately 55-65% VO2max. Capillaries were identified histologically and fiber types determined using adenosinetriphosphatase (ATPase) histochemistry. Succinate dehydrogenase (SDH) activity and CSA in individual fibers were measured using a computerized image analysis system. Exercise training did not increase (P > 0.05) the capillary-to-fiber ratio for any fiber type. However, training significantly decreased CSA (P < 0.05) and increased capillary density (capillary number/CSA) (P < 0.05) in type I, type IIa, and type IIb fibers. Furthermore, exercise training resulted in small but significant increase in SDH activity (P < 0.05) in type I and IIa fibers, whereas training did not alter SDH activity (P > 0.05) in type IIb fibers. These data demonstrate that endurance training in senescent animals results in small relative improvements in both oxidative capacity and capillary density in costal diaphragmatic type I and IIa muscle fibers. The increase in both capillary density and fiber SDH activity was largely due to a reduction in fiber CSA.


1998 ◽  
Vol 84 (6) ◽  
pp. 2183-2189 ◽  
Author(s):  
Akihiko Ishihara ◽  
Roland R. Roy ◽  
Yoshinobu Ohira ◽  
Yasuhiko Ibata ◽  
V. Reggie Edgerton

There have been no systematic comparisons of skeletal muscle adaptations in response to voluntary wheel running under controlled loading conditions. To accomplish this, a voluntary running wheel for rats and mice was developed in which a known load can be controlled and monitored electronically. Five-week-old male Sprague-Dawley rats (10 rats/group) were assigned randomly to either a 1) sedentary control group (Control); 2) voluntary exercised with no load (Run-No-Load) group; or 3) voluntary exercised with additional load (Run-Load) group for 8 wk. The load for the Run-Load group was progressively increased to reach ∼60% of body weight during the last week of training. The proportions of fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow oxidative (SO) fibers in the plantaris were similar in all groups. The absolute and relative plantaris weights were greater in the Run-Load group compared with the Control and Run-No-Load groups. The mean fiber cross-sectional areas of FG, FOG, and SO fibers were 20, 25, and 15% greater in the Run-Load than in Control rats. In addition, these fiber types were 16, 21, and 12% larger in Run-Load than in Run-No-Load rats. The muscle weights and mean cross-sectional areas of each fiber type were highly correlated with the average running distances and total work performed in the Run-Load, but not the Run-No-Load, group. The slope of the relationship between fiber size and running distance and total work performed was significant for each fiber type but was higher for FG and FOG fibers compared with SO fibers. These data show that the load on a rat running voluntarily can determine the magnitude of a hypertrophic response and the population of motor units that are recruited to perform at a given loading condition.


2020 ◽  
Vol 98 (11) ◽  
Author(s):  
Andrea M Gunawan ◽  
Con-Ning Yen ◽  
Brian T Richert ◽  
Allan P Schinckel ◽  
Alan L Grant ◽  
...  

Abstract Feeding ractopamine (RAC), a β-adrenergic agonist (BAA), to pigs increases type IIB muscle fiber type-specific protein and mRNA expression. However, increases in the abundance of these fast-twitch fiber types occur with other forms of muscle hypertrophy and thus BAA-induced changes in myosin heavy chain (MyHC) composition may simply be associated with increased muscle growth known to occur in response to BAA feeding. The objective of this study was to determine whether RAC feeding could change the MyHC gene expression in the absence of maximal muscle growth. Pigs were fed either an adequate diet that supported maximal muscle hypertrophy or a low nutrient diet that limited muscle growth. RAC was included in diets at 0 or 20 mg/kg for 1, 2, or 4 wk. Backfat depth was less (P &lt; 0.05) in pigs fed the low nutrient diet compared with the adequate diet but was not affected by RAC. Loin eye area was greater (P &lt; 0.05) in pigs fed an adequate diet plus RAC at 1 wk but did not differ among remaining pigs. At 2 and 4 wk, however, pigs fed the adequate diet had greater loin eye areas (P &lt; 0.05) than pigs fed the low nutrient diet regardless of RAC feeding. Gene expression of the MyHC isoforms, I, IIA, IIX, and IIB, as well as glycogen synthase, citrate synthase, β 1-adrenergic receptor (AR), and β 2-AR were determined in longissimus dorsi (LD) and red (RST) and white (WST) portions of the semitendinosus muscles. MyHC type I gene expression was not altered by RAC or diet. Feeding RAC decreased (P &lt; 0.01) MyHC type IIA gene expression in all muscles, but to a greater extent in WST and LD. MyHC type IIX gene expression was lower (P &lt; 0.05) in WST and LD muscles in response to RAC but was not altered in RST muscles. RAC increased (P &lt; 0.05) MyHC type IIB gene expression in all muscles, but to a greater extent in RST. β 1-AR gene expression was unaffected by RAC or diet, whereas the expression of the β 2-AR gene was decreased (P &lt; 0.001) by RAC. No significant RAC * diet interactions were observed in gene expression in this study, indicating that RAC altered MyHC and β 2-AR gene expression in porcine skeletal muscles independent of growth.


1983 ◽  
Vol 245 (2) ◽  
pp. H368-H374 ◽  
Author(s):  
I. H. Sarelius ◽  
L. C. Maxwell ◽  
S. D. Gray ◽  
B. R. Duling

We determined muscle fiber type and capillarity in cremaster muscle samples from rats and hamsters of different ages. Histochemical estimation of oxidative capacity was made from the activity of either nicotinamide dinucleotide tetrazolium reductase (NADH-TR) or succinic dehydrogenase (SDH), and fibers were termed fast or slow from myofibrillar ATPase activity. Fibers were classified as type I (low ATPase, high NADH-TR/SDH), type IIa (high ATPase, high SDH/NADH-TR), type IIb (high ATPase, low SDH/NADH-TR), or type IIc (no acid reversal of ATPase, high NADH-TR). Type IIb fibers accounted for 60-80% of the muscle area in both species at all ages. The principal change with maturation was muscle fiber hypertrophy. Mean cross-sectional fiber area increased from 488 +/- 70 (SE) and 453 +/- 19 micron2 in young hamsters and rats, respectively, to 1,255 +/- 99 and 1,540 +/- 101 micron2 in adults. Capillary density (no. of capillaries/mm2 tissue) paralleled fiber hypertrophy; it decreased significantly with maturation from 684 +/- 60 (SE) to 228 +/- 26/mm2 in hamsters and from 341 +/- 15 to 213 +/- 15/mm2 in rats. In vitro estimates of capillary density are compared with previously obtained in vivo data (31), and sources of error are identified. We conclude that reported differences in microvascular function in the cremaster muscle in vivo during maturation or between species cannot be ascribed to changes in muscle composition.


Author(s):  
Kaleen M. Lavin ◽  
Margaret B. Bell ◽  
Jeremy S. McAdam ◽  
Bailey D Peck ◽  
R. Grace Walton ◽  
...  

The skeletal muscle hypertrophic response to resistance exercise training (RT) is highly variable across individuals. The molecular underpinnings of this heterogeneity are unclear. This study investigated transcriptional networks linked to RT-induced muscle hypertrophy, classified as (i) predictive of hypertrophy, (ii) responsive to RT independent of muscle hypertrophy, or (iii) plastic with hypertrophy. Older adults (n=31, 18F/13M, 70±4y) underwent 14-wk RT (3d/wk, alternating high-low-high intensity). Muscle hypertrophy was assessed by pre- to post-RT change in mid-thigh muscle cross-sectional area (CSA) [computed tomography (CT), primary outcome], and thigh lean mass [dual-energy x-ray absorptiometry (DXA), secondary outcome]. Transcriptome-wide poly-A RNA-seq was performed on vastus lateralis tissue collected pre- (n=31) and post-RT (n=22). Prediction networks (using only baseline RNAseq) were identified by Weighted Gene Correlation Network Analysis (WGCNA). To identify Plasticity networks, WGCNA change indices for paired samples were calculated and correlated to changes in muscle size outcomes. Pathway-Level Information ExtractoR (PLIER) was applied to identify Response networks and link genes to biological annotation. Predictionnetworks (n=6) confirmed transcripts previously connected to resistance/ aerobic training adaptations in the MetaMEx database while revealing novel member genes that should fuel future research to understand the influence of baseline muscle gene expression on hypertrophy. Response networks (n=6) indicated RT-induced increase in aerobic metabolism and reduced expression of genes associated with spliceosome biology and type-I myofibers. A single exploratory Plasticity network was identified. Findings support that inter-individual differences in baseline gene expression may contribute more than RT-induced changes in gene networks to muscle hypertrophic response heterogeneity.


2002 ◽  
Vol 27 (4) ◽  
pp. 415-422 ◽  
Author(s):  
Michael R.M. Mcguigan ◽  
William J. Kraemer ◽  
Michael R. Deschenes ◽  
Scott E. Gordon ◽  
Takashi Kitaura ◽  
...  

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


1999 ◽  
Vol 87 (2) ◽  
pp. 634-642 ◽  
Author(s):  
Roland R. Roy ◽  
Steven R. Monke ◽  
David L. Allen ◽  
V. Reggie Edgerton

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.


2006 ◽  
Vol 100 (5) ◽  
pp. 1617-1622 ◽  
Author(s):  
Bharathi Aravamudan ◽  
Carlos B. Mantilla ◽  
Wen-Zhi Zhan ◽  
Gary C. Sieck

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.


2002 ◽  
Vol 92 (5) ◽  
pp. 2005-2011 ◽  
Author(s):  
Lori W. Smith ◽  
John D. Smith ◽  
David S. Criswell

The purpose of this study was to determine the necessity of nitric oxide (NO) for hypertrophy and fiber-type transition in overloaded (OL) skeletal muscle. Endogenous NO production was blocked by administering N G-nitro-l-arginine methyl ester (l-NAME; 0.75 mg/ml; ∼100 mg · kg−1 · day−1) in drinking water. Thirty-eight female Sprague-Dawley rats (∼250 g) were randomly divided into four groups: control-nonoverloaded (Non-OL), control-OL, l-NAME-Non-OL, andl-NAME-OL. Chronic overload of the plantaris was induced bilaterally by surgical removal of the gastrocnemius and soleus. Rats in the Non-OL groups received sham surgeries. l-NAME treatment began 24 h before surgery and continued until the rats were killed 14 days postsurgery. Although OL induced hypertrophy in both control (+76%) and l-NAME (+39%) conditions ( P < 0.05), mean plantaris-to-body mass ratio in thel-NAME-OL group was significantly lower ( P< 0.05) than that in the control-OL group. Microphotometric analysis of histochemically determined fiber types revealed increases in cross-sectional area ( P < 0.05) for all fiber types (types I, IIA, and IIB/X) in the OL plantaris from control rats, whereas l-NAME-OL rats exhibited increases only in type I and IIB/X fibers. SDS-PAGE analysis of myosin heavy chain (MHC) composition in the plantaris indicated a significant ( P< 0.05) OL effect in the control rats. Specifically, the mean proportion of type I MHC increased 6% ( P < 0.05), whereas the proportion of type IIb MHC decreased ∼9% ( P < 0.05). No significant OL effects on MHC profile were observed in the l-NAME rats. These data support a role of NO in overload-induced skeletal muscle hypertrophy and fiber-type transition.


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