Slow Oxidative Fibers Research Articles

Common errors in textbook descriptions of muscle fiber size in nontrained humans

Exercise science and human anatomy and physiology textbooks commonly report that type IIB muscle fibers have the largest cross-sectional area of the three fiber types. These descriptions of muscle fiber sizes do not match with the research literature examining muscle fibers in young adult nontrained humans. For men, most commonly type IIA fibers were significantly larger than other fiber types (six out of 10 cases across six different muscles). For women, either type I, or both I and IIA muscle fibers were usually significantly the largest (five out of six cases across four different muscles). In none of these reports were type IIB fibers significantly larger than both other fiber types. In 27 studies that did not include statistical comparisons of mean fiber sizes across fiber types, in no cases were type IIB or fast glycolytic fibers larger than both type I and IIA, or slow oxidative and fast oxidative glycolytic fibers. The likely reason for mistakes in textbook descriptions of human muscle fiber sizes is that animal data were presented without being labeled as such, and without any warning that there are interspecies differences in muscle fiber properties. Correct knowledge of muscle fiber sizes may facilitate interpreting training and aging adaptations.

How muscles define maximum running performance in lizards: an analysis using swing- and stance-phase muscles

Maximum locomotor performance is crucial for capturing prey, escaping predators and many other behaviors. However, we know little about what defines maximum performance in vertebrates. Muscles drive the movement of the limbs during locomotion, and thus likely play a major role in defining locomotor capacity. For lizards, the iliofibularis, a swing-phase muscle, is often linked to ecology and/or performance. However, stance-phase muscles likely limit performance given that they propel the animal. Using a small semi-arboreal lizard (Sceloporus woodi), we compared how swing- and stance-phase muscles relate to maximum running speed and acceleration. We employed both a level and vertical trackway to elicit ecologically relevant locomotor performance. Six individuals were filmed at 250 frames s⁻¹ in lateral view. Following performance trials, upper and lower hindlimbs were sectioned and assessed using histochemistry. Fast glycolytic, fast oxidative and slow oxidative fibers were detected and counted in the gastrocnemius (GA; stance phase) and iliofibularis (IF; swing phase) muscles. In addition, the mean fiber diameter for each fiber type in each muscle was determined, as was the fiber cross-sectional area. We found that properties of the GA, but not the IF, were positively correlated with performance. Interestingly, certain attributes of the GA were correlated with maximum vertical locomotion whereas others were correlated with maximum level locomotion. We conclude that stance phase, not swing phase, limits maximum performance in this species of lizard. In addition, we highlight the need to include properties of stance-phase muscles and a spectrum of ecologically relevant behaviors when attempting to correlate locomotor physiology with ecology and/or performance.

Modification of muscle inherent properties through age at slaughter, growth promotants and breed crosses

Girard, I., Aalhus, J. L., Basarab, J. A., Larsen, I. L. and Bruce, H. L. 2011. Modification of muscle inherent properties through age at slaughter, growth promotants and breed crosses. Can. J. Anim. Sci. 91: 635–648. A 2⁴ factorial experiment tested the interactions of slaughter age (12–13 or 18–20 mo), growth hormone use, β-adrenergic agonist (β-AA) use and breed cross [Hereford–Aberdeen Angus (HAA) or Charolais–Red Angus (CRA)] on the composition, fibre types, and connective tissue characteristics of m. semitendinosus (ST) and m. gluteus medius (GM) from 112 crossbred steers. Muscle weights increased with slaughter age, implantation and CRA genetics (P 0.10).Animal age increased fast glycolytic (FG) and decreased fast oxidative glycolytic (FOG) fibre percentages by 7.2 and 6.6%, respectively, in the ST and increased slow oxidative (SO) and FOG fibre areas in both muscles (P<0.05). Cross-sectional areas of all fibre types were increased in the ST with implantation. In the GM, implantation increased SO (3.1%) and reduced FOG (3.2%) fibre percentages, while RAC reduced the SO (3.8%) and increased the FG (6.1%) fibre percentages (P<0.05).Only GM total collagen content increased with slaughter age (P<0.05),but collagen solubility decreased with slaughter age for both muscles (P<0.05). CRA genetics increased FG percentage in the GM of yearling-fed steers and increased moisture and protein and reduced fat contents of both muscles (P<0.05). In the muscles studied, IMP, slaughter age and animal genetics induced greater changes in muscle inherent properties than RAC.

Fiber Type Conversion by PGC-1α Activates Lysosomal and Autophagosomal Biogenesis in Both Unaffected and Pompe Skeletal Muscle

PGC-1α is a transcriptional co-activator that plays a central role in the regulation of energy metabolism. Our interest in this protein was driven by its ability to promote muscle remodeling. Conversion from fast glycolytic to slow oxidative fibers seemed a promising therapeutic approach in Pompe disease, a severe myopathy caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA) which is responsible for the degradation of glycogen. The recently approved enzyme replacement therapy (ERT) has only a partial effect in skeletal muscle. In our Pompe mouse model (KO), the poor muscle response is seen in fast but not in slow muscle and is associated with massive accumulation of autophagic debris and ineffective autophagy. In an attempt to turn the therapy-resistant fibers into fibers amenable to therapy, we made transgenic KO mice expressing PGC-1α in muscle (tgKO). The successful switch from fast to slow fibers prevented the formation of autophagic buildup in the converted fibers, but PGC-1α failed to improve the clearance of glycogen by ERT. This outcome is likely explained by an unexpected dramatic increase in muscle glycogen load to levels much closer to those observed in patients, in particular infants, with the disease. We have also found a remarkable rise in the number of lysosomes and autophagosomes in the tgKO compared to the KO. These data point to the role of PGC-1α in muscle glucose metabolism and its possible role as a master regulator for organelle biogenesis - not only for mitochondria but also for lysosomes and autophagosomes. These findings may have implications for therapy of lysosomal diseases and other disorders with altered autophagy.

Changes in metabolic profile and population of skeletal muscle fibers of mice overexpressing calsequestrin: Influence of losartan

In heart failure, exertional fatigue of skeletal muscles can occur. A transgenic mouse overexpressing calsequestrin can be regarded as an animal model of heart failure. The aims of the present study were to investigate, whether at the time of cardiac failure the composition of fiber types of skeletal muscles was altered, what kind of alterations in glycolytic and oxidative enzyme activities occurred in different muscle fiber types and whether these were affected by the administration of the angiotensin II receptor blocker, losartan. Hemodynamic parameters were determined using a working heart preparation. Four groups of mice were investigated: wild-type (WT) mice and transgenic (TG) mice overexpressing calsequestrin, with and without losartan treatment. Enzyme activities were measured in homogenates of Rectus femoris muscle and in muscle fibers, which were typed by their metabolic profile. Calcineurin expression was measured by Western blotting. Succinate dehydrogenase activity was increased by 275% in R. femoris muscle homogenates of TG compared to WT mice. This was due to a 57% increase in slow oxidative fibers, which was accompanied by an increased calcineurin expression in TG muscles. This increase was attenuated by losartan treatment. With respect to glycerol-3-phosphate-dehydrogenase (GPDH), no difference was evident comparing WT and TG. Treatment with losartan resulted in a down-regulation of GPDH in WT and TG. In conclusion, changes in skeletal muscles occur in this mouse model of heart failure and these changes were antagonized by losartan. In contrast to heart failure patients, in the mouse model a shift to the oxidative phenotype of skeletal muscle was noted, possibly due to enhanced calcineurin expression.

Specific fibre composition and metabolism of the rectus abdominis muscle of bovine Charolais cattle.

BackgroundAn important variability of contractile and metabolic properties between muscles has been highlighted. In the literature, the majority of studies on beef sensorial quality concerns M. longissimus thoracis. M. rectus abdominis (RA) is easy to sample without huge carcass depreciation and may appear as an alternative to M. longissimus thoracis for fast and routine physicochemical analysis. It was considered interesting to assess the muscle fibres of M. rectus abdominis in comparison with M. longissimus thoracis (LT) and M. triceps brachii (TB) on the basis of metabolic and contractile properties, area and myosin heavy chain isoforms (MyHC) proportions. Immuno-histochemical, histochemical, histological and enzymological techniques were used. This research concerned two populations of Charolais cattle: RA was compared to TB in a population of 19 steers while RA was compared to LT in a population of 153 heifers.ResultsRA muscle had higher mean fibre areas (3350 μm2 vs 2142 to 2639 μm2) than the two other muscles. In RA muscle, the slow-oxidative fibres were the largest (3957 μm2) and the fast-glycolytic the smallest (2868 μm2). The reverse was observed in TB muscle (1725 and 2436 μm2 respectively). In RA muscle, the distinction between fast-oxidative-glycolytic and fast-glycolytic fibres appeared difficult or impossible to establish, unlike in the other muscles. Consequently the classification based on ATPase and SDH activities seemed inappropriate, since the FOG fibres presented rather low SDH activity in this muscle in comparison to the other muscles of the carcass. RA muscle had a higher proportion of I fibres than TB and LT muscles, balanced by a lower proportion either of IIX fibres (in comparison to TB muscle) or of IIA fibres (in comparison to LT muscle). However, both oxidative and glycolytic enzyme activities were lower in RA than in TB muscle, although the LDH/ICDH ratio was higher in RA muscle (522 vs 340). Oxidative enzyme activities were higher in RA than in LT muscle, whereas glycolytic enzyme activity was lower. In RA muscle, contractile and metabolic properties appeared to be less well-correlated than in the two other muscles.ConclusionsRA muscle has some particularities in comparison to the LT and TB muscles, especially concerning the unusual large cross-section surface of SO fibres and the very low oxidative activity of intermediate IIA fibres.

Temporal expression of TnI fast and slow isoforms in biceps femoris and masseter muscle during pig growth

Biceps femoris (BF) and masseter muscle (MM) are the mixture of slow oxidative and fast-twitch fibres. Compared with MM, BF had the significantly higher expression of myosin heavy chain (MyHC) fast IIx and IIb isoforms (MyHCIIx and MyHCIIb), but lower expression of MyHC slow isoform (MyHCI) and fast IIa isoform (MyHCIIa). The objective of this study was to investigate the expression pattern of troponin I (TnI) slow-twitch isoform (TNNI1) and fast-twitch isoform (TNNI2) in BF and MM of Yorkshire and Meishan pigs which differed significantly in the growth rate. The expression of the TNNI1 and TNNI2 peaked at the postnatal 35 days in Yorkshire pigs and postnatal 60 days in Meishan pigs. The expression of TNNI1 and TNNI2 in Meishan pigs was significantly higher than that in Yorkshire pigs at the foetal 60 days, while the opposite occurred at postnatal 35 days. The expression ratio of TNNI1 relative to TNNI2 favoured TNNI2 expression in BF and MM regardless of Yorkshire and Meishan pigs. TNNI1 expression in MM was significantly higher than that in BF at 60, 120 and 180 days in Meishan pigs and at 120 and 180 days in Yorkshire pigs. On the contrary, no significant difference of TNNI2 expression in BF and MM was found except for Yorkshire pigs of 180 days. This study provided the foundation for future research on TnI isoforms as the model gene to study mechanisms of muscle fibre-specific gene regulation in pigs.

Muscle unloading potentiates the effects of acetyl‐L‐carnitine on the slow oxidative muscle phenotype

The effect of acetyl-L-carnitine (ALCAR) supplementation to 3-month-old rats in normal-loading and unloading conditions has been here investigated by a combined morphological, biochemical and transcriptional approach to test whether ALCAR might cause a remodeling of the metabolic/contractile phenotype of soleus muscle. Morphological assessment demonstrated an increase of type I oxidative fiber content and cross-sectional area in ALCAR-treated animals both in normal-loading and in unloading conditions. ALCAR prevented loss of mitochondrial mass in unloaded animals whereas no ALCAR-dependent increase of mitochondrial mass occurred in normal-loaded muscle. Validated microarray analysis delineated an ALCAR-induced maintenance of a slow-oxidative expression program only in unloaded soleus muscle. Indeed, the muscle adjustment of the expression profile of factors underlying mitochondrial oxidative metabolism, protein turnover, fiber type differentiation and an adaptation of voltage-gated ion channel expression was distinguishable with respect to the loading status. This selectivity may suggest a key role of muscle loading status in the manifestation of ALCAR effects. The results extend to a broader level of biological informations the previous notion on ALCAR positive effect in rat soleus muscle during unloading and point to a role of ALCAR for the maintenance of its slow-oxidative fiber character.

Profiling Muscle-Specific MicroRNA Expression after Peripheral Denervation and Reinnervation in a Rat Model

MicroRNAs (miRNAs) are a class of highly conserved, non-coding RNAs involved in post-transcriptional gene regulation. The muscle-specific miRNAs, miR-1, miR-133a, and miR-206, are expressed in skeletal muscles and have been shown to contribute to muscle development. To profile their expression after sciatic nerve denervation and reinnervation, the soleus muscles of the rats were analyzed with quantitative real-time PCR at 1 week, 1 month, 2 months, and 4 months after the experiments. In addition, a combined approach using computational prediction by the miRanda website and the Agilent Whole Rat Genome 4 x 44 k oligo microarray experiment was performed to investigate the potential target genes of these three miRNAs in the denervated and reinnervated muscles. The results revealed that with the first downregulation of miR-1 and miR-133a within 1 month in the denervated muscle, the expression of miR-1 and miR-133 increased by approximately 2-fold at 4 months after denervation and reinnervation; on the other hand, the expression of miR-206 was significantly increased to approximately 3-fold 1 month later only following reinnervation but not following denervation, and lasted at least for 4 months. The expression pattern of miR-206 was different from that of miR-1 and miR-133a. Notably, two genes (Hnrpu and Npy) and one gene (Ptprd) were potentially regulated both in the denervated and reinnervated muscle by miR-1 and miR-133a, respectively. There were six potential target genes (Hnrpu, Lsamp, MGC108776, Mef2, Npy, and Ppfibp2) of the upregulated miR-206 in the reinnervated muscle. Among these, three (Hnrpu, Npy, and MGC108776) were potentially regulated by both miR-1 and miR-206. Because the Mef2 transcription factor was reported to promote the transformation of type II fast glycolytic fibers into type I slow oxidative fibers, the upregulation of miR-206 with decreased expression of the Mef2 transcript in the 4 month reinnervated muscle, which presented type II fiber predominance 4 months after nerve microanastomosis, might indicate the role of miR-206 in determining the fiber type after peripheral nerve regeneration.

Influence of feeding regime and finishing system on lamb muscle fiber and meat quality

The study verified the influence of different nutritional levels of the dams, before parturition, the weaning age of the lambs and the finishing system on lamb muscle fiber morphology and meat quality. Ile-de-France × Bergamacia crossbred dams grazing on natural grassland were divided into two groups: 1) nutritional supplement 30 days before the parturition (SUPL), and 2) no nutritional supplement (NS). These groups were further subdivided by weaning age of the lambs, which corresponded to either 45 or 60 days. The weaned lambs from each of the previous groups were also divided into different finishing systems: confined and fed a complete diet (CD), confined and fed hay (H) and kept on grassland (P). The lambs were slaughtered at 30 kg live weight (CD and P), or at 150 days of age (H). The carcasses were cooled at 4ºC/24h. The analyzed variables were: longissimus dorsi muscle fiber morphophysiology, post mortem myofibrillar fragmentation (at 0, 3 and 7 days post mortem), meat pH and temperature. There was no effect of supplementation of dams or weaning age of the lambs for the evaluated variables. The frequency of slow-oxidative (SO), fast-oxidative-glycolytic (FOG) and fast-glycolytic (FG) muscle fiber types was not altered by the treatments, but the fiber cross-sectional area was smaller for the lambs finished only on hay, and the meat pH values and temperature were lower and the myofibrill fragment dimensions were smaller. As time maturation increased from 0 to 3 and 7 days post mortem, there was a decrease in the length of the myofibrill fragments. The diet of the lambs which were maintained confined and fed only with hay was nutritionally inferior when compared with all the others, and this changed the quality of the meat compared to the finishing systems on grassland or confined and fed complete diet.

Fiber type homogeneity of the flight musculature in small birds

Studies of medium- and large-bodied avian species have suggested that variation in flight muscle composition is related to differences in flight behavior. For example, slow-twitch or tonic fibers are generally found only in the flight muscles of non-volant or soaring/gliding birds. However, we know comparatively little about fiber composition of the muscles of the smallest birds. Here we describe the fiber composition of muscles from the wings, shoulders, and legs of two small avian species, which also display very high wingbeat frequencies: Anna's hummingbirds (Calypte anna) and zebra finches (Taeniopygia guttata). All flight muscles examined in both species contained exclusively fast oxidative glycolytic (FOG) fibers. These unique results suggest that fast oxidative fibers are both necessary and sufficient for the full range of flight behaviors in these small-bodied birds. Like all other studied birds, the zebra finch gastrocnemius, a tarsometatarsal extensor, contained a mixture of FOG (27.1%), slow oxidative (SO, 12.7%), and fast glycolytic (FG, 60.2%) fibers. By contrast, the hummingbird gastrocnemius lacked FG fibers (85.5% FOG, 14.5% SO), which may reflect the reduced role of the hindlimb during take-off. We further hypothesize that thermogenic requirements constrain fiber type heterogeneity in these small endothermic vertebrates.

Associations of Serum Adiponectin with Skeletal Muscle Morphology and Insulin Sensitivity

Skeletal muscle morphology and function are strongly associated with insulin sensitivity. The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (beta, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (beta, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (beta, -0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (beta difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (beta difference, -0.053; 95% confidence interval -0.107, -0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.

Why is α-Actinin-3 Deficiency So Common in the General Population? The Evolution of Athletic Performance

'We can now explain how this common genetic variation influences athletic performance as well as why it has become so common in the general population. There is a fascinating link between factors that influence survival in ancient humans and the factors that contribute to athletic abilities in modern man.' The human ACTN3 gene encodes the protein alpha-actinin-3, a component of the contractile apparatus in fast skeletal muscle fibers. In 1999, we identified a common polymorphism in ACTN3 (R577X) that results in absence of alpha-actinin-3 in more than one billion people worldwide, despite the ACTN3 gene being highly conserved during human evolution. In 2003, we demonstrated that ACTN3 genotype influences elite athletic performance, and the association between ACTN3 genotype and skeletal muscle performance has since been replicated in athletes and non-athlete cohorts. We have also studied the evolution of the R577X allele during human evolution and demonstrated that the null (X) allele has undergone strong, recent positive selection in Europeans and Asian populations. We have developed an Actn3 knockout mouse model that replicates alpha-actinin-3 deficiency in humans and has already provided insight into the role of alpha-actinin-3 in the regulation of skeletal muscle metabolism, fibre size, muscle mass and contractile properties. In particular, mouse muscle lacking alpha-actinin-3 uses energy more efficiently, with the fast fibers displaying metabolic and contractile properties of slow oxidative fibers. While this favors endurance activities, the trade off is that the muscle cannot generate the rapid contractions needed to excel in sprinting. We propose that the shift towards more efficient aerobic muscle metabolism associated with alpha-actinin-3 deficiency also underlies the adaptive benefit of the 577X allele. Our future studies will focus on the effect of ACTN3 genotype on response to exercise and ageing, and the onset and severity of muscle disease phenotype.

Meta-analysis of the effect of animal maturity on muscle characteristics in different muscles, breeds, and sexes of cattle

The effect of animal maturity on fiber cross-sectional area, percentage of fiber types, activities of isocitrate dehydrogenase (ICDH) and lactate dehydrogenase (LDH), total and insoluble collagen and lipid concentration was investigated in the longis-simus thoracis (LT), semitendinosus (ST), and triceps brachii (TB) muscles. The analysis considered 2,642 muscle samples from bulls, steers, and cows of Aubrac, Charolais, Limousin, Montbéliard, and Salers breeds. For the bulls, the fiber cross-sectional area, percentage of slow oxidative fibers, and ICDH activity showed a quadratic relationship (P < 0.05), and the percentage of fast oxidative-glycolytic and fast glycolytic fibers and LDH activity showed a cubic relationship (P < 0.05) with increased maturity. A linear relationship was observed for the collagen and lipid muscle characteristics. The response equation coefficients for different muscles indicate that development of muscle characteristics is different for each muscle. Compared with the other muscles, ST muscle had a greater fiber cross-sectional area, proportion of fast glycolytic fibers, LDH activity, and collagen content. The LT muscle had a greater proportion of slow-oxidative fibers and lipid (P < 0.05). Within the ST muscle, all characteristics except lipid concentration showed different development between the breeds. Steers showed greater changes in muscle fiber cross-sectional area, percentage of fast oxidative-glycolytic and fast glycolytic fibers, and total lipid in the muscle with increasing maturity compared with bulls. The mean fiber cross-sectional area and percentage of fast glycolytic fibers was greater and the mean lipid concentration was less in bulls compared with steers (P < 0.05). Data for cows were from more mature animals. Muscle characteristics in cows did not show large changes with increasing degree of maturity. Muscle type accounts for a greater proportion of the variation in the muscle characteristics than breed and sex of the animal.

Fiber-specific responses of muscle glycogen repletion in fasted rats physically active during recovery from high-intensity physical exertion

Mild physical activity performed immediately after a bout of intense exercise in fasting humans results in net glycogen breakdown in their slow oxidative (SO) muscle fibers and glycogen repletion in their fast twitch (FT) fibers. Because several animal species carry a low proportion of SO fibers, it is unclear whether they can also replenish glycogen in their FT fibers under these conditions. Given that most skeletal muscles in rats are poor in SO fibers (<5%), this issue was examined using groups of 24-h fasted Wistar rats (n=10) that swam for 3 min at high intensity with a 10% weight followed by either a 60-min rest (passive recovery, PR) or a 30-min swim with a 0.5% weight (active recovery, AR) preceding a 30-min rest. The 3-min sprint caused 61-79% glycogen fall across the muscles examined, but not in the soleus (SOL). Glycogen repletion during AR without food was similar to PR in the white gastrocnemius (WG), where glycogen increased by 71%, and less than PR in both the red and mixed gastrocnemius (RG, MG). Glycogen fell by 26% during AR in the SOL. Following AR, glycogen increased by 36%, 87%, and 37% in the SOL, RG, and MG, respectively, and this was accompanied by the sustained activation of glycogen synthase and inhibition of glycogen phosphorylase in the RG and MG. These results suggest that mammals with a low proportion of SO fibers can also replenish the glycogen stores of their FT fibers under extreme conditions combining physical activity and fasting.

Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited

We previously reported an "athlete's paradox" in which endurance-trained athletes, who possess a high oxidative capacity and enhanced insulin sensitivity, also have higher intramyocellular lipid (IMCL) content. The purpose of this study was to determine whether moderate exercise training would increase IMCL, oxidative capacity of muscle, and insulin sensitivity in previously sedentary overweight to obese, insulin-resistant, older subjects. Twenty-five older (66.4 +/- 0.8 yr) obese (BMI = 30.3 +/- 0.7 kg/m2) men (n = 9) and women (n = 16) completed a 16-wk moderate but progressive exercise training program. Body weight and fat mass modestly but significantly (P < 0.01) decreased. Insulin sensitivity, measured using the euglycemic hyperinsulinemic clamp, was increased (21%, P = 0.02), with modest improvements (7%, P = 0.04) in aerobic fitness (Vo2peak). Histochemical analyses of IMCL (Oil Red O staining), oxidative capacity [succinate dehydrogenase activity (SDH)], glycogen content, capillary density, and fiber type were performed on skeletal muscle biopsies. Exercise training increased IMCL by 21%. In contrast, diacylglycerol and ceramide, measured by mass spectroscopy, were decreased (n = 13; -29% and -24%, respectively, P < 0.05) with exercise training. SDH (19%), glycogen content (15%), capillary density (7%), and the percentage of type I slow oxidative fibers (from 50.8 to 55.7%), all P < or = 0.05, were increased after exercise. In summary, these results extend the athlete's paradox by demonstrating that chronic exercise in overweight to obese older adults improves insulin sensitivity in conjunction with favorable alterations in lipid partitioning and an enhanced oxidative capacity within muscle. Therefore, several key deleterious effects of aging and/or obesity on the metabolic profile of skeletal muscle can be reversed with only moderate increases in physical activity.

Reply to Padilla, Hamilton, Lundgren, Mckenzie, and Mickleborough

LETTERS TO THE EDITORReply to Padilla, Hamilton, Lundgren, Mckenzie, and MickleboroughJoffrey Zoll, Elodie Ponsot, Stephane Dufour, and Martin FlückJoffrey Zoll, Elodie Ponsot, Stephane Dufour, and Martin FlückPublished Online:01 Aug 2007https://doi.org/10.1152/japplphysiol.00535.2007MoreSectionsPDF (112 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat To the Editor: We appreciate the interest of Padilla et al. (3) in our results showing the effect of a modified intermittent hypoxic training (IHT) in endurance athletes. Although the authors raise several comments, the main scientific question seems to concern the rationale to investigate the transcript level for carbonic anhydrase 3 (CA3) in the skeletal muscles of our athletes.To clarify this issue, it is worth bearing in mind that the study was not specifically performed to identify muscular markers of hypoxia exposure. Rather, the objective was to highlight adaptations of athletes' skeletal muscle after performing specific hypoxia training sessions. We did not, therefore, primarily intend to describe the effects of chronic or acute hypoxia alone, as in the two studies cited by Padilla et al. Consequently, we explored the respective muscular transcript levels of genes involved in mitochondrial biogenesis, redox regulation, and glucose uptake to ascertain whether they could participate in the improvement of endurance performance following 6-wk IHT.We chose to trace mRNA of CA3 because this enzyme is considered as a potential factor of mitochondrial flux improvement and because high cytosolic concentrations of CA3 have been reported in mammalian skeletal muscle type I (slow-oxidative fibers; Ref. 1). Its RNA level also showed significant plasticity with muscle atrophy and reloading (2). Although our data point out an involvement of CA3 to the hypoxia adaptation of muscle, there is certainly a need to study other carbonic anhydrase isoforms, which could play a role in the muscular adaptations following IHT.Nevertheless, we thank Padilla et al. for their thorough review of our papers, which gives us the opportunity to explain some of their concerns and to correct one mistake that unfortunately appeared on Fig. 2 in the third part of the trilogy.1) A total of 18 volunteered subjects completed the research protocol (6-wk training program, pre- and post-training muscle biopsies of the vastus lateralis muscle and treadmill performance evaluations). As regularly reported in invasive human studies, biopsies did not always give us enough biological material to carry out the measurements of mitochondrial function and mRNAs expression, explaining why the population decline to 15 subjects in the second and third part of our work (4, 5).2) By not specifying the interaction effect, our aim was to simplify the result sections of the papers, which already report an important amount of data.3) The range of values for Tlim in the printed Fig. 2 does not make sense as presented. We apologize for this mistake we did not notice and provide the exact, double-checked, correlations with the actual range of values.In conclusion, CA3 is possibly not the best marker of hypoxia exposure, but we demonstrate that this isoenzyme of CA is specifically upregulated in hypoxia-trained subjects and presumably plays a role, together with other factors, in the ultimate improvement of endurance performance capacity. Download figureDownload PowerPointREFERENCES1 Geers C, Gros G. Carbon dioxide transport and carbonic anhydrase in blood and muscle. Physiol Rev 80: 681–715, 2000.Link | ISI | Google Scholar2 Fluck M, Schmutz S, Wittwer M, Hoppeler H, Desplanches D. Transcriptional reprogramming during reloading of atrophied rat soleus muscle. Am J Physiol Regul Integr Comp Physiol 289: R4–R14, 2005.Link | ISI | Google Scholar3 Padilla J, Hamilton S, Lundgren E, Mckenzie J, Mickleborough T. Exercise training in normobaric hypoxia: is carbonic anyhdrase III the best marker of hypoxia? J Appl Physiol. doi:10.1152/japplphysiol.00408.2007.Google Scholar4 Ponsot E, Dufour SP, Zoll J, Doutrelau S, N'Guessan B, Geny B, Hoppeler H, Lampert E, Mettauer B, Ventura-Clapier R, Richard R. Exercise training in normobaric hypoxia in endurance runners. II. Improvement of mitochondrial properties in skeletal muscle. J Appl Physiol 100: 1249–1257, 2006.Link | ISI | Google Scholar5 Zoll J, Ponsot E, Dufour S, Doutreleau S, Ventura-Clapier R, Vogt M, Hoppeler H, Richard R, Fluck M. Exercise training in normobaric hypoxia in endurance runners. III. Muscular adjustments of selected gene transcripts. J Appl Physiol 100: 1258–1266, 2006.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: J. Zoll, Institut de Physiologie, Faculté de Médecine, 4, rue Kirschleger, F-67085 Strasbourg Cedex, France (e-mail: [email protected]) Download PDF Previous Back to Top FiguresReferencesRelatedInformation More from this issue > Volume 103Issue 2August 2007Pages 731-732 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00535.2007History Published online 1 August 2007 Published in print 1 August 2007 Metrics

Calcineurin differentially regulates fast myosin heavy chain genes in oxidative muscle fibre type conversion

In skeletal muscle, calcineurin is crucial for myocyte differentiation and in the determination of the slow oxidative fibre phenotype, both processes being important determinants of muscle performance, metabolic health and meat-animal production. Fibre type is defined by the isoform identity of the skeletal myosin heavy chain (MyHC). We have examined the responses of the major MyHC genes to calcineurin signalling during fibre formation of muscle C2C12 cells. We have found that calcineurin acts as a signal to up-regulate the fast-oxidative MyHC2a gene and to down-regulate the faster MyHC2x and MyHC2b genes in a manner that appears to be NFAT-independent. Contrary to expectation, the up-regulation of MyHCslow by calcineurin seems to be time-dependent and is only detectable once the initial differential expression of the post-natal fast MyHC genes has been established. The simultaneous elevated expression of MyHC2a and the repression of MyHC2x and MyHC2b expression indicate that both processes (elevation and repression) are actively coordinated during oxidative fibre conversion. We have further determined that muscle LIM protein (MLP), a calcineurin-binding Z-line co-factor, is induced by calcineurin and that its co-expression with calcineurin has an additive effect on MyHCslow expression. Hence, post-natal fast MyHCs are important early effector targets of calcineurin, whereas MyHCslow up-regulation is mediated in part by calcineurin-induced MLP.

To breathe or not to breathe: the respiratory muscles and COPD

The respiratory muscles are unique among skeletal muscles in that they are required to work without sustained rest throughout life. It is not surprising, therefore, that the ventilatory pump has been the subject of intense investigation over the past 30 years, with particular interest in the ability

Horse soleus muscle: Postural sensor or vestigial structure?

The soleus muscle of horses is rather diminutive with respect to the overall size of adjacent synergist muscles in the hind limb of the horse. Whether or not such a muscle might be vestigial or may be providing some essential function has not been determined. We have studied the horse's soleus muscle using histochemical (ATPase), immunocytochemical (myosin isoform identification), and SDS-PAGE analysis to demonstrate that it is largely composed of 100% type I, presumed slow-twitch fibers. Only one soleus muscle studied (out of 13 adult horses) contained any type II muscle fibers. Given this consistent high percentage of slow-oxidative fibers, we hypothesized that the soleus muscle could have a significant role in proprioceptive function, essentially functioning as a proprioceptive organ instead of a significant force-generating muscle during locomotion. We tested this by examining three whole soleus muscles and assessing their muscle spindle content, which proved to have a spindle index of about 12. This value provided equivocal support for the hypothesis since it did not approach values reported for other mammalian proprioceptive muscles that were approximately 40-50 spindles per gram of muscle mass. Other parameters, such as motoneuron number and muscle unit size, may be useful in understanding these data.