Muscle Fiber Type Distribution Research Articles

The reproducibility of different metabolic markers for muscle fiber type distributions investigated by functional 31P-MRS during dynamic exercise

PurposeThe objective of the study was to investigate the reproducibility of exercise induced pH-heterogeneity by splitting of the inorganic phosphate (Pi) signal in the corresponding 31P-MRS spectra and to compare results of this approach with other fiber-type related markers, like phosphocreatine/adenosine triphosphate (PCr/ATP) ratio, and PCr-recovery parameters. Material and methodsSubjects (N=3) with different sportive background were tested in 10 test sessions separated by at least 3 days. A MR-compatible pedal ergometer was used to perform the exercise and to induce a pH-based splitting of the Pi-signal in 31P-MR spectra of the medial gastrocnemius muscle. The PCr recovery was analyzed using a non-negative least square algorithm (NNLS) and multi-exponential regression analysis to estimate the number of non-exponential components as well as their amplitude and time constant. The reproducibility of the estimated metabolic marker and the resulting fiber-type distributions between the 10 test sessions were compared. ResultsThe reproducibility (standard deviation between measurements) based on (1) Pi components varied from 2% to 4%, (2) PCr recovery time components varied from 10% to 12% and (3) phosphate concentrations at rest varied from 8% to 11% between test sessions. Due to the sportive activity differences between the 3 subjects were expected in view of fiber type distribution. All estimated markers indicate the highest type I percentage for volunteer 3 medium for volunteer 2 and the lowest for volunteer 1. ConclusionsThe relative high reproducibility of pH dependent Pi components during exercise indicates a high potential of this method to estimate muscle fiber-type distributions in vivo. To make this method usable not only to detect differences in muscle fiber distributions but also to determine individual fiber-type volume contents it is therefore recommended to validate this marker by histological methods and to reveal the effects of muscle fiber recruitments and fiber-type specific Pi concentrations on the intensity ratios between the splitted Pi-components.

The mechanistic bases of the power-time relationship: muscle metabolic responses and relationships to muscle fibre type.

The power-asymptote (critical power; CP) of the hyperbolic power-time relationship for high-intensity exercise defines a threshold between steady-state and non-steady-state exercise intensities and the curvature constant (W') indicates a fixed capacity for work >CP that is related to a loss of muscular efficiency. The present study reports novel evidence on the muscle metabolic underpinnings of CP and W' during whole-body exercise and their relationships to muscle fibre type. We show that the W' is not correlated with muscle fibre type distribution and that it represents an elevated energy contribution from both oxidative and glycolytic/glycogenolytic metabolism. We show that there is a positive correlation between CP and highly oxidative type I muscle fibres and that muscle metabolic steady-state is attainable <CP but not >CP. Our findings indicate a mechanistic link between the bioenergetic characteristics of muscle fibre types and the power-time relationship for high-intensity exercise. We hypothesized that: (1) the critical power (CP) will represent a boundary separating steady-state from non-steady-state muscle metabolic responses during whole-body exercise and (2) that the CP and the curvature constant (W') of the power-time relationship for high-intensity exercise will be correlated with type I and type IIx muscle fibre distributions, respectively. Four men and four women performed a 3min all-out cycling test for the estimation of CP and constant work rate (CWR) tests slightly >CP until exhaustion (Tlim ), slightly <CP for 24min and until the >CP Tlim isotime to test the first hypothesis. Eleven men performed 3min all-out tests and donated muscle biopsies to test the second hypothesis. Below CP, muscle [PCr] [42.6±7.1vs. 49.4±6.9mmol(kgd.w.)(-1) ], [La(-) ] [34.8±12.6vs. 35.5±13.2mmol(kgd.w.)(-1) ] and pH (7.11±0.08 vs. 7.10±0.11) remained stable between ∼12 and 24min (P>0.05 for all), whereas these variables changed with time >CP such that they were greater [[La(-) ] 95.6±14.1mmol(kgd.w.)(-1) ] and lower [[PCr] 24.2±3.9mmol(kgd.w.)(-1) ; pH 6.84±0.06] (P<0.05) at Tlim (740±186s) than during the <CP trial. The CP (234±53W) was correlated with muscle type I (r=0.67, P=0.025) and inversely correlated with muscle type IIx fibre proportion (r=-0.76, P=0.01). There was no relationship between W' (19.4±6.3kJ) and muscle fibre type. These data indicate a mechanistic link between the bioenergetic characteristics of different muscle fibre types and the power-duration relationship. The CP reflects the bioenergetic characteristics of highly oxidative type I muscle fibres, such that a muscle metabolic steady-state is attainable below and not above CP.

The effect of one-week intensive feed restriction and age on the carcass composition and meat quality of growing rabbits

The effect of one-week intensive feed restriction on the carcass characteristics, meat tenderness, cooking loss, and muscle fibre characteristics of growing rabbits was evaluated. Weaned rabbits (35 days) were divided into three groups: rabbits fed ad libitum (ADL), rabbits fed 50 g (R50), and rabbits fed 65 g (R65) of feed per animal per day in days 42-49 of age. Dressing out percentage was lower (-1.3% and -2.3% for R50 and R65, respectively) in restricted rabbits (P ≤ 0.001) but increased with age (P ≤ 0.001). Cooking loss signifi- cantly increased in restricted rabbits. A significant interaction between feeding regime and age was observed in the number of type αR muscle fibres, the highest number (P ≤ 0.05) was observed in the ADL rabbits (114.5) at 49 days, and the lowest was found in the R50 group at 70 days of age (25.0). Feed restriction increased the percentage of αW glycolytic fibres (P ≤ 0.01). A significant negative correlation was found between cooking loss and the cross sectional area of αW fibres (-0.486) and αR (-0.325). It could be concluded that one-week intensive feed restriction did not have a negative effect on meat tenderness and cooking loss, despite the fact that it affected muscle fibre type distribution.

Dietary Nitrate (NO3−)‐Induced Increases in Skeletal Muscle Contractile Function: High vs. Low Responders

We have recently reported that acute ingestion of dietary NO3−, an important source of nitric oxide (NO) via the enterosalivary pathway, increases the maximal speed and power of skeletal muscle in healthy individuals, in athletes, and in patients with systolic heart failure. This ergogenic effect is hypothesized to be the result of NO‐mediated stimulation of soluble guanyl cyclase and hence production of cyclic GMP. However, consistent with studies of the effects of dietary NO3− on blood pressure or aerobic exercise performance, not all of the subjects we studied previously demonstrated comparable improvements in muscle speed and/or power. In the present investigation we sought to identify factors contributing to this interindividual variability. Eighteen healthy subjects (12 men and 6 women) ranging in age from 22 to 79 (mean 48±20) y were studied used a randomized, double‐blind, placebo‐controlled, crossover design. On one occasion, subjects were tested 2 h after ingesting a concentrated beetroot juice (BRJ) supplement containing 11.2 mmol NO3−. On another, they were tested 2 h after ingesting BRJ depleted of NO3− (placebo). Breath NO was measured periodically as an indicator of NO bioavailability, and muscle contractility was assessed using isokinetic dynamometry. For all subjects combined, dietary NO3− increased (P&lt;0.05) peak knee extensor torque, and hence power, at 6.28 rad/s (~½maximal velocity; Vmax) from 6.38±2.16 to 6.53±2.33 W/kg, or by 2.4%. Individual changes, however, ranged from −21.5 to +26.8%, with 14 of 18 subjects being positive “responders”. This interindividual variability was not significantly correlated with age (i.e., r=−0.19; P=0.45), with in vivo indicators of muscle fiber type distribution, i.e., baseline Vmax (i.e., r=0.10; P=0.68) or fatigability (i.e., r=−0.14; P=0.58), or with the increase in breath NO in either absolute (i.e., r=−0.21; P=0.41) or relative (i.e., r=−0.18; P=0.46) terms. In contrast, significant positive correlations were observed between the magnitude of the dietary nitrate NO3− ‐induced increase in power and female sex (i.e., r=0.53; P=0.02) and dose of NO3−/kg of body mass (i.e., r=0.47; P=0.05). However, the latter correlation appears to have simply been the result of the women being lighter on average, as there was no correlation between the relative improvement in muscle power and dose of NO3−/kg of body mass when the men (i.e., r=0.14; P=0.66) or women (i.e., r=0.26; P=0.62) were analyzed separately. We conclude that the magnitude of the dietary NO3− ‐induced increase in muscle power is independent of age, baseline muscle function, or increase in whole‐body NO bioavailability, but that women generally benefit more than men. The effect of NO3− dose on muscle speed and power, on the other hand, awaits further study.Support or Funding InformationResearch reported in this publication was supported by the Barnes‐Jewish Hospital Foundation, the Washington University Mentors in Medicine and C‐STAR programs, and Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.

Skeletal muscle fiber size and fiber type distribution in human cancer: Effects of weight loss and relationship to physical function

Cancer patients frequently experience weight loss, with negative consequences for functionality and prognosis. The extent to which muscle atrophy contributes to weight loss, however, is not clear, as few studies have directly measured muscle fiber morphology in cancer patients. Whole body and regional tissue composition were measured, along with the cross-sectional area (CSA) and fiber type of mechanically-isolated, single muscle fibers, in 19 cancer patients (8 with a history of weight loss, 11 weight-stable) and 15 non-diseased controls. Whole body fat mass was reduced in cancer patients with a history of weight loss, but no differences in whole body or leg fat-free mass were apparent. In contrast, reductions (∼20%) in single muscle fiber CSA were found in both slow-twitch, myosin heavy chain (MHC) I and fast-twitch, MHC IIA fibers in both weight-stable patients and those with a history of weight loss. Fiber type distribution showed a shift towards a fast-twitch phenotype compared to controls, which may preserve muscle function in cancer patients despite atrophy, as positive relationships were found between the fractions of hybrid MHC IIAX and I/IIA fibers and 6-min walk performance. Our results suggest that, although not apparent from whole body or regional measurements, cancer is associated with reduced skeletal muscle fiber size independent of weight loss history and a shift towards fast-twitch fibers, phenotypes that resemble adaptations to muscle disuse.

Prolyl hydroxylase domain 2 deficiency promotes skeletal muscle fiber-type transition via a calcineurin/NFATc1-dependent pathway.

BackgroundHypoxia exposure is known to induce an alteration in skeletal muscle fiber-type distribution mediated by hypoxia-inducible factor (HIF)-α. The downstream pathway of HIF-α leading to fiber-type shift, however, has not been elucidated. The calcineurin pathway is one of the pathways responsible for slow muscle fiber transition. Because calcineurin pathway is activated by vascular endothelial growth factor (VEGF), one of the factors induced by HIF-1α, we hypothesized that the stabilization of HIF-1α may lead to slow muscle fiber transition via the activation of calcineurin pathway in skeletal muscles. To induce HIF-1α stabilization, we used a loss of function strategy to abrogate Prolyl hydroxylase domain protein (PHD) 2 responsible for HIF-1α hydroxylation making HIF-1α susceptible to ubiquitin dependent degradation by proteasome. The purpose of this study was therefore to examine the effect of HIF-1α stabilization in PHD2 conditional knockout mouse on skeletal muscle fiber-type transition and to elucidate the involvement of calcineurin pathway on muscle fiber-type transition.ResultsPHD2 deficiency resulted in an increased capillary density in skeletal muscles due to the induction of vascular endothelial growth factor. It also elicited an alteration of skeletal muscle phenotype toward the type I fibers in both of the soleus (35.8 % in the control mice vs. 46.7 % in the PHD2-deficient mice, p < 0.01) and the gastrocnemius muscle (0.94 vs. 1.89 %, p < 0.01), and the increased proportion of type I fibers appeared to correspond to the area of increased capillary density. In addition, calcineurin and nuclear factor of activated T cell (NFATc1) protein levels were increased in both the gastrocnemius and soleus muscles, suggesting that the calcineurin/NFATc1 pathway was responsible for the type I fiber transition regardless of PGC-1α, which responded minimally to PHD2 deficiency. Indeed, we found that tacrolimus (FK-506), a calcineurin inhibitor, successfully suppressed slow fiber-type formation in PHD2-deficient mice.ConclusionsTaken together, stabilized HIF-1α induced by PHD2 conditional knockout resulted in the transition of muscle fibers toward a slow fiber type via a calcineurin/NFATc1 signaling pathway. PHD2 conditional knockout mice may serve as a model for chronic HIF-1α stabilization as in mice exposed to low oxygen concentration.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-016-0079-5) contains supplementary material, which is available to authorized users.

Fiber Typing of the Erector Spinae and Multifidus Muscles in Healthy Controls and Back Pain Patients: A Systematic Literature Review

ObjectiveUnderstanding the changes in muscle fiber typing is relevant in the context of muscle disorders because it provides information on the metabolic profile and functional capacity. The aim of this study was to systematically review the literature comparing muscle fiber typing in the back muscles of healthy subjects with low back pain (LBP) patients. MethodsPredefined keywords regarding muscle fiber typing and back muscles were combined in PubMed and Web of Science electronic search engines from inception to August 2014. Full-text articles were independently screened by 2 independent, blinded researchers. Full texts fulfilling the predefined inclusion criteria were assessed on risk of bias by 2 independent researchers, and relative data were extracted. Data were not pooled because of heterogeneity in biopsy locations and population. ResultsFrom the 214 articles that were identified, 18 met the inclusion criteria. These articles evaluated the muscle fiber type distribution or proportional fiber type area between muscles, muscle layers, men, and women or healthy subjects and LBP patients. Regarding muscle fiber type distribution, findings in healthy subjects and LBP patients show no or inconclusive evidence for intermuscular and interindividual differentiation. Studies evaluating the proportional fiber type area also suggest little intermuscular differentiation but provide plausible evidence that the proportional area occupied by type I fibers is higher in women compared to men. The evidence for differentiation based on the presence of low back pain is conflicting. ConclusionThis study found that the evidence regarding muscle fiber typing in back muscles is either inconclusive or shows little differences. The most plausible evidence exists for differentiation in proportional fiber type area depending on sex.

Immunohistochemical analysis of orbicularis oris muscle fiber distribution at the philtrum in healthy infants

ObjectiveTo characterize the fiber-type distribution of the orbicularis oris muscle at the philtrum in healthy infants by immunohistochemistry and examine the relationship between orbicularis oris and philtrum structure. MethodsSamples of the upper lip were obtained from two infant cadavers. Serial sagittal sections were obtained at the midline of the philtral dimple, unilateral philtral ridge, and the lateral side. Three sections from each site were prepared for immunohistochemical staining using myosin heavy chain fast fiber (MHCf) and myosin heavy chain slow fiber (MHCs) antibodies to determine the ratio of fast to slow skeletal muscle fibers. ResultsThe ratio of fast to slow muscle fibers differed significantly among the superficial orbicularis oris muscle (98.30%:1.13%), deep pars peripheralis (95.30%:3.14%), and deep pars marginalis (91.31%:5.74%), with a significantly higher percentage of slow fibers in the pars marginalis compared to pars peripheralis (P=0.002) and fast fibers in the superficial muscle compared to pars marginalis and peripheralis (both P=0.000). Similarly, the fast:slow fiber ratio differed among the superficial philtral dimple (95.88%:2.41%), superficial philtral ridge (98.52%:1.11%), and superficial midlateral philtral ridge (99.07%:0.66%), with a higher percentage of fast fibers higher on the lateral side of the superficial philtral ridge than at the philtral ridge (P=0.030) and higher at the philtral ridge than the philtral dimple (P=0.001). The fast:slow fiber ratio did not differ within the pars peripheralis at the philtral dimple (93.94%:4.19%), philtral ridge (94.49%:3.84%), and lateral philtral ridge (95.79%:2.70%) (all P>0.05). ConclusionsPhiltum structure is likely determined in part by the distribution of muscle fiber types among philtral dimple, ridge, and lateral side. These differences should be considered in cleft lip repair.

Biology of Muscle Atrophy and of its Recovery by FES in Aging and Mobility Impairments: Roots and By-Products.

There is something in our genome that dictates life expectancy and there is nothing that can be done to avoid this; indeed, there is not yet any record of a person who has cheated death. Our physical prowess can vacillate substantially in our lifetime according to our activity levels and nutritional status and we may fight aging, but we will inevitably lose. We have presented strong evidence that the atrophy which accompanies aging is to some extent caused by loss of innervation. We compared muscle biopsies of sedentary seniors to those of life long active seniors, and show that these groups indeed have a different distribution of muscle fiber diameter and fiber type. The senior sportsmen have many more slow fiber-type groupings than the sedentary people which provides strong evidence of denervation-reinnervation events in muscle fibers. It appears that activity maintains the motoneurons and the muscle fibers. Premature or accelerated aging of muscle may occur as the result of many chronic diseases. One extreme case is provided by irreversible damage of the Conus and Cauda Equina, a spinal cord injury (SCI) sequela in which the human leg muscles may be completely and permanently disconnected from the nervous system with the almost complete disappearance of muscle fibers within 3-5 years from SCI. In cases of this extreme example of muscle degeneration, we have used 2D Muscle Color CT to gather data supporting the idea that electrical stimulation of denervated muscles can retain and even regain muscle. We show here that, if people are compliant, atrophy can be reversed. A further example of activity-related muscle adaptation is provided by the fact that mitochondrial distribution and density are significantly changed by functional electrical stimulation in horse muscle biopsies relative to those not receiving treatment. All together, the data indicate that FES is a good way to modify behaviors of muscle fibers by increasing the contraction load per day. Indeed, it should be possible to defer the muscle decline that occurs in aging people and in those who have become unable to participate in physical activities. Thus, FES should be considered for use in rehabilitation centers, nursing facilities and in critical care units when patients are completely inactive even for short periods of time.

Deletion of Kinin B2 Receptor Alters Muscle Metabolism and Exercise Performance.

Metabolic syndrome is a cluster of metabolic risk factors such as obesity, diabetes and cardiovascular diseases. Mitochondria is the main site of ATP production and its dysfunction leads to decreased oxidative phosphorylation, resulting in lipid accumulation and insulin resistance. Our group has demonstrated that kinins can modulate glucose and lipid metabolism as well as skeletal muscle mass. By using B2 receptor knockout mice (B2R-/-) we investigated whether kinin action affects weight gain and physical performance of the animals. Our results show that B2R-/- mice are resistant to high fat diet-induced obesity, have higher glucose tolerance as well as increased mitochondrial mass. These features are accompanied by higher energy expenditure and a lower feed efficiency associated with an increase in the proportion of type I fibers and intermediary fibers characterized by higher mitochondrial content and increased expression of genes related to oxidative metabolism. Additionally, the increased percentage of oxidative skeletal muscle fibers and mitochondrial apparatus in B2R-/- mice is coupled with a higher aerobic exercise performance. Taken together, our data give support to the involvement of kinins in skeletal muscle fiber type distribution and muscle metabolism, which ultimately protects against fat-induced obesity and improves aerobic exercise performance.

Preserved muscle oxidative metabolic phenotype in newly diagnosed non‐small cell lung cancer cachexia

BackgroundCachexia augments cancer-related mortality and has devastating effects on quality of life. Pre-clinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype (OXPHEN) stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate the presence of muscle OXPHEN loss in newly diagnosed patients with lung cancer, especially in those with cachexia.MethodsQuadriceps muscle biopsies of comprehensively phenotyped pre-cachectic (n = 10) and cachectic (n = 16) patients with non-small cell lung cancer prior to treatment were compared with healthy age-matched controls (n = 22). OXPHEN was determined by assessing muscle fibre type distribution (immunohistochemistry), enzyme activity (spectrophotometry), and protein expression levels of mitochondrial complexes (western blot) as well as transcript levels of (regulatory) oxidative genes (quantitative real-time PCR). Additionally, muscle fibre cross-sectional area (immunohistochemistry) and systemic inflammation (multiplex analysis) were assessed.ResultsMuscle fibre cross-sectional area was smaller, and plasma levels of interleukin 6 were significantly higher in cachectic patients compared with non-cachectic patients and healthy controls. No differences in muscle fibre type distribution or oxidative and glycolytic enzyme activities were observed between the groups. Mitochondrial protein expression and gene expression levels of their regulators were also not different.ConclusionMuscle OXPHEN is preserved in newly diagnosed non-small cell lung cancer and therefore not a primary trigger of cachexia in these patients.

Vitamin D3, 25‐Hydroxyvitamin D3, and 1α‐Hydroxyvitamin D3 Modulate Fiber Type Distribution in Bicep Femoris of Growing Rats

An experiment was conducted to examine the effects of different types of vitamin D3 on skeletal muscle development using growing rats. Three‐week‐old rats were fed a vitamin D3‐deficient diet for 4 weeks and vitamin D3‐replete diets for the next 4 weeks as each of vitamin D3 (vit D3, 1,000 IU/kg diet), 25‐hydroxyvitamin D3 (25‐OH D3, 400 IU/kg diet), and 1α‐hydroxyvitamin D3 (1α‐OH D3, 4 IU/kg diet) was supplemented. Negative control group was fed a vitamin D3‐deficient diet, and positive control group was fed a vitamin D3‐supplemented diet (1,000 IU/kg diet) for the whole experimental period, 8 weeks. In results, body weight, feed intake, and body composition (lean and fat) were not affected by vitamin D3 dose and type. Quantitative gene expression of skeletal muscle differentiation markers (MyoD, Myogenin, Mrf4, Myf5, and Myostatin) also showed no difference. However, skeletal muscle fiber type distribution (myofibrillar ATPase staining) was changed in bicep femoris (BF) of the rats fed different types of vitamin D3 supplements.In positive control, type I was increased by 2.4 fold (7.22 % vs. 2.95 %) compared to negative control. In the rats fed vit D3‐replete diets followed by 4‐weeks of vitamin D3 deficiency, both type I and IIa were increased only 1.3 fold (3.72% vs. 2.95%, and 20.79 % vs. 15.74 %) compared to negative control. Percentages of type I were 5.0‐ and 6.9‐fold increased in BF of the rats fed 25‐OH D3 (14.63 % vs. 2.95%) and 1α‐OH D3 (20.45 % vs. 2.95 %) respectively, in comparison to negative control. The present study demonstrates that vitamin D3 does not affect lean growth, but it might mediate skeletal muscle fiber type distribution in growing rats depending on the vitamin D3 types.

Therapeutic physical exercise in neural injury: friend or foe?

[Purpose] The intensity of therapeutic physical exercise is complex and sometimes controversial in patients with neural injuries. This review assessed whether therapeutic physical exercise is beneficial according to the intensity of the physical exercise. [Methods] The authors identified clinically or scientifically relevant articles from PubMed that met the inclusion criteria. [Results] Exercise training can improve body strength and lead to the physiological adaptation of skeletal muscles and the nervous system after neural injuries. Furthermore, neurophysiological and neuropathological studies show differences in the beneficial effects of forced therapeutic exercise in patients with severe or mild neural injuries. Forced exercise alters the distribution of muscle fiber types in patients with neural injuries. Based on several animal studies, forced exercise may promote functional recovery following cerebral ischemia via signaling molecules in ischemic brain regions. [Conclusions] This review describes several types of therapeutic forced exercise and the controversy regarding the therapeutic effects in experimental animals versus humans with neural injuries. This review also provides a therapeutic strategy for physical therapists that grades the intensity of forced exercise according to the level of neural injury.

Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity.

It has become increasingly apparent that substrate metabolism is subject to gender-specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic–euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole-body insulin sensitivity and in particular insulin-stimulated glucose uptake of skeletal muscle. Whether an eventual higher insulin sensitivity of female skeletal muscle can be related to gender-specific regulation of molecular metabolism will be topic for discussion. Gender differences in muscle fiber type distribution and substrate availability to and in skeletal muscle are highly relevant for substrate metabolism in men and women. In particular, the molecular machinery for glucose and fatty acid oxidative and storage capacities in skeletal muscle and its implications for substrate utilization during metabolic situations of daily living are discussed, emphasizing their relevance for substrate choice in the fed and fasted state, and during periods of physical activity and recovery. Together, handling of carbohydrate and lipids and regulation of their utilization in skeletal muscle have implications for whole-body glucose homeostasis in men and women. 17-β estradiol is the most important female sex hormone, and the identification of estradiol receptors in skeletal muscle has opened for a role in regulation of substrate metabolism. Also, higher levels of circulating adipokines as adiponectin and leptin in women and their implications for muscle metabolism will be considered.

G.P.205: A modified cysteine knot ligand trap of the TGFβ superfamily, ACE-083, increases muscle mass locally in a mouse model of Duchenne muscular dystrophy

To investigate a new therapeutic strategy for inherited asymmetrical myopathies, we generated a modified cysteine knot ligand trap of TGFβ superfamily members, ACE-083, which acts locally to increase skeletal muscle mass. ACE-083 binds to activin and myostatin and inhibits their signaling. Unlike ActRIIB-Fc, ACE-083 does not bind to ligands BMP9/10. To demonstrate the ability of ACE-083 to increase muscle mass locally, we used a murine model of muscular dystrophy. Six week old C57BL/10ScCN-Dmd^mdx/J (mdx) and wild-type mice received intramuscular injections into the left gastrocnemius muscle of ACE-083 (100μg, 50μL, biw) or vehicle (PBS, 50μL, biw) for 4weeks. Each injection corresponded to a dose of approximately 5mg/kg. After 4weeks of treatment muscles were collected to evaluate the effect of ACE-083. In the left gastrocnemius muscle injected with 100μg ACE-083, mdx mice had increased muscle mass 16% (<i>p</i><0.01) and wild-type mice 34% (<i>p</i><0.001) compared to the non-injected, contralateral legs. Histologically, muscles injected with ACE-083 underwent hypertrophy with no signs of hyperplasia and no alteration in muscle fiber type distribution. Over the course of the study there were no significant differences in body weight between ACE-083 or vehicle treated mice. In addition, pectoral and femoris muscles were examined to determine if there was a systemic effect of locally-administered ACE-083. There was no significant increase in muscle size in the pectoral (<i>p</i>=0.838) or the femoris (<i>p</i>=0.62) muscles in either treatment group. Furthermore, we determined there was no active ACE-083 in the serum following local injections, minimizing potential off target effects in other organs. These preclinical results demonstrate that ACE-083 can effectively increase muscle mass locally following direct injection into target muscles. Therefore, local inhibition of activin and myostatin using ACE-083 represents a promising therapeutic approach for the treatment of asymmetric myopathies.

Muscle Fibre Type Distribution of the Thoracolumbar and Hindlimb Regions of Horses: Relating Fibre Type and Functional Role

IntroductionThe muscle fibre type (MFT) of the deep epaxial musculature has not been determined in horses. The objective was to determine the MFT distribution in selected muscles of thoracolumbar and hindlimb region of horses. This included deep epaxial and hypaxial muscles that were hypothesised to have a postural stabilising role. A second objective was to examine differences in MFT distribution between Arabians and Quarter horses.MethodsMuscle biopsy samples (114) were obtained from 5 Quarter horses, 4 Arabians, and 2 Thoroughbreds. The myosin heavy chain distribution was determined by gel electrophoresis. Mann‐Whitney rank test was used to compare the proportional MFT content and differences between breeds.ResultsMm. sacrocaudalis dorsalis medialis and diaphragm had the highest proportion of MFT‐I, 84.1% (±18.4) and 72.4% (±12.5), respectively. The remaining deep epaxial muscles and the hypaxial m. psoas minor had approximately equal MFT‐I and II proportions. Mm. psoas major, iliocostalis, longissimus dorsi and the hind limb muscles contained mostly MFT‐IIX: from 50.5% (±12.8) to 67.9% (±7.3). Quarter horses had significantly more MFT‐IIX in m. psoas major 60.8% (±9.1) than Arabians 41.9% (±3.2). Arabians had significantly more MFT‐I fibres in m. longissimus dorsi 16.9% (±4.6) than Quarter horses 9.9% (±1.4) (P&lt;0.05).ConclusionsThe MFT distribution of the deep epaxial muscles, mm. psoas minor and diaphragm, suggest a postural stabilizing role in contrast to the fibre type proportions of the hindlimb muscles. The findings can direct diagnosis, prevention and treatment of muscular or neuromotor dysfunction in the thoracolumbar and hind limb area.Ethical Animal ResearchThe study was approved by the University of Queensland Animal Ethics Committee. Explicit owner informed consent for participation in this study is not stated. Sources of funding: none. Competing interests: none.

Fibre type‐specific satellite cell response to aerobic training in sedentary adults

In the present study, we sought to determine the effect of a traditional, 12 week aerobic training protocol on skeletal muscle fibre type distribution and satellite cell content in sedentary subjects. Muscle biopsies were obtained from the vastus lateralis [n = 23 subjects (six male and 17 female); body mass index 30.7 ± 1.2 kg m(-2)] before and after 12 weeks of aerobic training performed on a cycle ergometer. Immunohistochemical analyses were used to quantify myosin heavy chain (MyHC) isoform expression, cross-sectional area and satellite cell and myonuclear content. Following training, a decrease in MyHC hybrid type IIa/IIx fibre frequency occurred, with a concomitant increase in pure MyHC type IIa fibres. Pretraining fibre type correlated with body mass index, and the change in fibre type following training was associated with improvements in maximal oxygen consumption. Twelve weeks of aerobic training also induced increases in mean cross-sectional area in both MyHC type I and type IIa fibres. Satellite cell content was also increased following training, specifically in MyHC type I fibres, with no change in the number of satellite cells associated with MyHC type II fibres. With the increased satellite cell content following training, an increase in myonuclear number per fibre also occurred in MyHC type I fibres. Hypertrophy of MyHC type II fibres occurred without detectable myonuclear addition, suggesting that the mechanisms underlying growth in fast and slow fibres differ. These data provide intriguing evidence for a fibre type-specific role of satellite cells in muscle adaptation following aerobic training.

Effect of dietary zinc and ractopamine hydrochloride on pork chop muscle fiber type distribution, tenderness, and color characteristics1,2

A total of 320 finishing pigs (PIC 327 × 1050; initially 98 kg) were used to determine the effects of adding Zn to diets containing ractopamine HCl (RAC) on muscle fiber type distribution, fresh chop color, and cooked meat characteristics. Dietary treatments were fed for approximately 35 d and consisted of a corn-soybean meal-based negative control (CON), a positive control diet with 10 mg/kg of RAC (RAC+), and the RAC+ diet plus 75, 150, or 225 mg/kg added Zn from either ZnO or Availa-Zn. Loins randomly selected from each treatment (n = 20) were evaluated using contrasts: CON vs. RAC+, interaction of Zn level × source, Zn level linear and quadratic polynomials, and Zn source. There were no Zn source effects or Zn source × level interactions throughout the study (P > 0.10). Pigs fed RAC+ had increased (P < 0.02) percentage type IIX and a tendency for increased (P = 0.10) percent type IIB muscle fibers. Increasing added Zn decreased (linear, P = 0.01) percentage type IIA and tended to increase (P = 0.09) IIX muscle fibers. On d 1, 2, 3, 4, and 5 of display, pork chops from pigs fed the RAC+ treatment had greater (P < 0.03) L* values compared to the CON. On d 0 and 3 of display, increasing added Zn tended to decrease (quadratic, P = 0.10) L* values and decreased (quadratic, P < 0.03) L* values on d 1, 2, 4, and 5. Pigs fed RAC+ had decreased (P < 0.05) a* values on d 1 and 4 of display and tended to have decreased (P < 0.10) a* values on d 0 and 2 compared to CON pork chops. Pork chops from the RAC+ treatment had a tendency for increased (P < 0.08) oxymyoglobin percentage compared to CON pork chops on d 1, 2, 4, and 5. On d 0, as dietary Zn increased in RAC+ diets, there was a decrease (linear, P < 0.01) in the formation of pork chop surface oxymyoglobin percentage. Metmyoglobin reducing ability (MRA) of pork chops on d 5 was decreased in the RAC+ group. Chops from pigs fed added Zn had increased (quadratic, P < 0.03) MRA on d 3 and 5 of the display period. There was a trend for increased (linear, P = 0.07) cooking loss with increasing Zn in RAC diets and treatments did not affect tenderness as measured by Warner-Bratzler shear force (P > 0.07). In conclusion, RAC+ diets produced chops that were lighter and less red but maintained a greater percentage of surface oxymyoglobin throughout a 5-d simulated retail display. Ractopamine reduced MRA at the end of the display period, but supplementing Zn to RAC diets restored MRA to near CON treatment levels at the end of the display period.

Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction

Heart failure (HF) with preserved ejection fraction (HFPEF) is the most common form of HF in older persons. The primary chronic symptom in HFPEF is severe exercise intolerance, and its pathophysiology is poorly understood. To determine whether skeletal muscle abnormalities contribute to their severely reduced peak exercise O2 consumption (Vo2), we examined 22 older HFPEF patients (70 ± 7 yr) compared with 43 age-matched healthy control (HC) subjects using needle biopsy of the vastus lateralis muscle and cardiopulmonary exercise testing to assess muscle fiber type distribution and capillarity and peak Vo2. In HFPEF versus HC patients, peak Vo2 (14.7 ± 2.1 vs. 22.9 ± 6.6 ml·kg(-1)·min(-1), P < 0.001) and 6-min walk distance (454 ± 72 vs. 573 ± 71 m, P < 0.001) were reduced. In HFPEF versus HC patients, the percentage of type I fibers (39.0 ± 11.4% vs. 53.7 ± 12.4%, P < 0.001), type I-to-type II fiber ratio (0.72 ± 0.39 vs. 1.36 ± 0.85, P = 0.001), and capillary-to-fiber ratio (1.35 ± 0.32 vs. 2.53 ± 1.37, P = 0.006) were reduced, whereas the percentage of type II fibers was greater (61 ± 11.4% vs. 46.3 ± 12.4%, P < 0.001). In univariate analyses, the percentage of type I fibers (r = 0.39, P = 0.003), type I-to-type II fiber ratio (r = 0.33, P = 0.02), and capillary-to-fiber ratio (r = 0.59, P < 0.0001) were positively related to peak Vo2. In multivariate analyses, type I fibers and the capillary-to-fiber ratio remained significantly related to peak Vo2. We conclude that older HFPEF patients have significant abnormalities in skeletal muscle, characterized by a shift in muscle fiber type distribution with reduced type I oxidative muscle fibers and a reduced capillary-to-fiber ratio, and these may contribute to their severe exercise intolerance. This suggests potential new therapeutic targets in this difficult to treat disorder.

Striated muscle fiber size, composition, and capillary density in diabetes in relation to neuropathy and muscle strength 糖尿病患者的横纹肌纤维尺寸、成份以及毛细血管密度与神经病变以及肌肉强度相关

Diabetic polyneuropathy (DPN) leads to progressive loss of muscle strength in the lower extremities due to muscular atrophy. Changes in vascularization occur in diabetic striated muscle; however, the relationship between these changes and DPN is as yet unexplored. The aim of the present study was to evaluate histologic properties and capillarization of diabetic skeletal muscle in relation to DPN and muscle strength. Twenty type 1 and 20 type 2 diabetic (T1D and T2D, respectively) patients underwent biopsy of the gastrocnemic muscle, isokinetic dynamometry at the ankle, electrophysiological studies, clinical examination, and quantitative sensory examinations. Muscle biopsies were stained immunohistochemically and muscle fiber diameter, fiber type distribution, and capillary density determined. Twenty control subjects were also included in the study. No relationship was found between muscle fiber diameter, muscle fiber type distribution, or capillary density and degree of neuropathy or muscle strength for either patient group. Muscle fiber diameter and the proportion of Type II fibers were greater for T1D patients than both T2D patients and controls. The T2D patients had fewer capillaries per muscle fiber than T1D patients and controls. Striated muscle fiber size, muscle fiber distribution, and vascularization are unrelated to DPN and muscle strength in diabetes.