Insulin-stimulated glucose uptake (GU) by skeletal muscle is enhanced several hours after acute exercise in rats with normal or reduced insulin sensitivity. Skeletal muscle is composed of multiple ...fiber types, but exercise's effect on fiber type-specific insulin-stimulated GU in insulin-resistant muscle was previously unknown. Male rats were fed a high-fat diet (HFD; 2 wk) and were either sedentary (SED) or exercised (2-h exercise). Other, low-fat diet-fed (LFD) rats remained SED. Rats were studied immediately postexercise (IPEX) or 3 h postexercise (3hPEX). Epitrochlearis muscles from IPEX rats were incubated in 2-deoxy-
Hglucose (2-
HDG) without insulin. Epitrochlearis muscles from 3hPEX rats were incubated with 2-
HDG ± 100 µU/ml insulin. After single fiber isolation, GU and fiber type were determined. Glycogen and lipid droplets (LDs) were assessed histochemically. GLUT4 abundance was determined by immunoblotting. In HFD-SED vs. LFD-SED rats, insulin-stimulated GU was decreased in type IIB, IIX, IIAX, and IIBX fibers. Insulin-independent GU IPEX was increased and glycogen content was decreased in all fiber types (types I, IIA, IIB, IIX, IIAX, and IIBX). Exercise by HFD-fed rats enhanced insulin-stimulated GU in all fiber types except type I. Single fiber analyses enabled discovery of striking fiber type-specific differences in HFD and exercise effects on insulin-stimulated GU. The fiber type-specific differences in insulin-stimulated GU postexercise in insulin-resistant muscle were not attributable to a lack of fiber recruitment, as indirectly evidenced by insulin-independent GU and glycogen IPEX, differences in multiple LD indexes, or altered GLUT4 abundance, implicating fiber type-selective differences in the cellular processes responsible for postexercise enhancement of insulin-mediated GLUT4 translocation.
Summary Background & aims 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. Methods 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. Results 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. Conclusions 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.
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•Puerarin ameliorates muscle wasting in type 1 diabetic rats.•Puerarin improves skeletal muscle weight and strength in type 1 diabetic rats.•Puerarin promotes transformation of muscle ...fiber types from slow-twitch to fast-twitch in type 1 diabetic rats.•Puerarin activates Akt/mTOR while inhibites autophagy in skeletal muscle.
Puerarin is an isoflavonoid extracted from Pueraria lobate with extensive pharmacological effects in traditional Chinese medicine. The evidence implicates that puerarin mitigates hyperglycemia and various relevant complications. Here, the effect of puerarin on skeletal muscle wasting induced by type 1 diabetes (T1D) was explored. Streptozotocin (STZ)-induced T1D male Sprague Dawley (SD) rats were used in this study. Muscle strength, weight and size were measured. L6 rat skeletal muscle cells were applied for in vitro study. Our results showed that eight-week oral puerarin administration (100 mg/kg) increased muscle strengths and weights accompanied by enhanced skeletal muscle cross-sectional areas in diabetic rats. Simultaneously, puerarin also reduced expressions of several muscle wasting marker genes including F-box only protein 32 (Atrogin-1) and muscle-specific RING-finger 1 (Murf-1) in diabetic group both in vitro and in vivo. Transformation from type I fibers (slow muscle) to type II fibers (fast muscle) were also observed under puerarin administration in diabetic rats. Puerarin promoted Akt/mTOR while inhibited LC3/p62 signaling pathway in skeletal muscle cells. In conclusion, our study showed that puerarin mitigated skeletal muscle wasting in T1D rats and closely related with Akt/mTOR activation and autophagy inhibition. Whether this effect in murine applies to humans remains to be determined.
Estrogen-related receptor γ (ERRγ) regulates the perinatal switch to oxidative metabolism in the myocardium. We wanted to understand the significance of induction of ERRγ expression in skeletal ...muscle by exercise. Muscle-specific VP16ERRγ transgenic mice demonstrated an increase in exercise capacity, mitochondrial enzyme activity, and enlarged mitochondria despite lower muscle weights. Furthermore, peak oxidative capacity was higher in the transgenics as compared with control littermates. In contrast, mice lacking one copy of ERRγ exhibited decreased exercise capacity and muscle mitochondrial function. Interestingly, we observed that increased ERRγ in muscle generates a gene expression profile that closely overlays that of red oxidative fiber-type muscle. We further demonstrated that a small molecule agonist of ERRβ/γ can increase mitochondrial function in mouse myotubes. Our data indicate that ERRγ plays an important role in causing a shift toward slow twitch muscle type and, concomitantly, a greater capacity for endurance exercise. Thus, the activation of this nuclear receptor provides a potential node for therapeutic intervention for diseases such as obesity, which is associated with reduced oxidative metabolism and a lower type I fiber content in skeletal muscle.
Adult skeletal muscles in vertebrates are composed of different types of myofibers endowed with distinct metabolic and contraction speed properties. Genesis of this fiber-type heterogeneity during ...development remains poorly known, at least in mammals. Six1 and Six4 homeoproteins of the Six/sine oculis family are expressed throughout muscle development in mice, and Six1 protein is enriched in the nuclei of adult fast-twitch myofibers. Furthermore, Six1/Six4 proteins are known to control the early activation of fast-type muscle genes in myocytes present in the mouse somitic myotome. Using double Six1:Six4 mutants (SixdKO) to dissect in vivo the genesis of muscle fiber-type heterogeneity, we analyzed here the phenotype of the dorsal/epaxial muscles remaining in SixdKO. We show by electron microscopy analysis that the absence of these homeoproteins precludes normal sarcomeric organization of the myofiber leading to a dystrophic aspect, and by immunohistochemistry experiments a deficiency in synaptogenesis. Affymetrix transcriptome analysis of the muscles remaining in E18.5 SixdKO identifies a major role for these homeoproteins in the control of genes that are specifically activated in the adult fast/glycolytic myofibers, particularly those controlling Ca2+ homeostasis. Absence of Six1 and Six4 leads to the development of dorsal myofibers lacking expression of fast-type muscle genes, and mainly expressing a slow-type muscle program. The absence of restriction of the slow-type program during the fetal period in SixdKO back muscles is associated with a decreased HDAC4 protein level, and subcellular relocalization of the transcription repressor Sox6. Six genes thus behave as essential global regulators of muscle gene expression, as well as a central switch to drive the skeletal muscle fast phenotype during fetal development.
► Genetic and embryologic origin of muscle fiber-type diversity remains unknown in mammals. ► We investigate the role of Six proteins in the genetic of muscle fiber-type diversity. ► We establish the gene network controlled by Six1/4 proteins in mouse E18 embryo. ► Six control crosstalk between slow and fast type determinant genes. ► Six are required for genesis of muscle fiber type diversity during embryogenesis.
Whilst calsequestrin (CSQ) is widely recognized as the primary Ca 2+ buffer in the sarcoplasmic reticulum (SR) in skeletal muscle fibres, its total buffering capacity and importance have come
into ...question. This study quantified the absolute amount of CSQ isoform 1 (CSQ1, the primary isoform) present in rat extensor
digitorum longus (EDL) and soleus fibres, and related this to their endogenous and maximal SR Ca 2+ content. Using Western blotting, the entire constituents of minute samples of muscle homogenates or segments of individual
muscle fibres were compared with known amounts of purified CSQ1. The fidelity of the analysis was proven by examining the
relative signal intensity when mixing muscle samples and purified CSQ1. The CSQ1 contents of EDL fibres, almost exclusively
type II fibres, and soleus type I fibres SOL (I) were, respectively, 36 ± 2 and 10 ± 1 μmol (l fibre volume) â1 , quantitatively accounting for the maximal SR Ca 2+ content of each. Soleus type II SOL (II) fibres (â¼20% of soleus fibres) had an intermediate amount of CSQ1. Every SOL (I)
fibre examined also contained some CSQ isoform 2 (CSQ2), which was absent in every EDL and other type II fibre except for
trace amounts in one case. Every EDL and other type II fibre had a high density of SERCA1, the fast-twitch muscle sarco(endo)plasmic
reticulum Ca 2+ -ATPase isoform, whereas there was virtually no SERCA1 in any SOL (I) fibre. Maximal SR Ca 2+ content measured in skinned fibres increased with CSQ1 content, and the ratio of endogenous to maximal Ca 2+ content was inversely correlated with CSQ1 content. The relative SR Ca 2+ content that could be maintained in resting cytoplasmic conditions was found to be much lower in EDL fibres than in SOL (I)
fibres (â¼20 versus >60%). Leakage of Ca 2+ from the SR in EDL fibres could be substantially reduced with a SR Ca 2+ pump blocker and increased by adding creatine to buffer cytoplasmic ADP at a higher level, both results indicating that
at least part of the Ca 2+ leakage occurred through SERCA. It is concluded that CSQ1 plays an important role in EDL muscle fibres by providing a large
total pool of releasable Ca 2+ in the SR whilst maintaining free Ca 2+ in the SR at sufficiently low levels that Ca 2+ leakage through the high density of SERCA1 pumps does not metabolically compromise muscle function.
Variations of fresh meat quality exist because the quality traits are affected by various intrinsic and extrinsic factors. Because the meat quality is basically dependent on muscle fiber ...characteristics, numerous studies have reported the relationship between quality traits and fiber characteristics. Despite intensive research, the relationship is yet to be fully established, however, the present knowledge suggests several potential ways to manipulate muscle fiber characteristics to improve meat quality. The present paper reviews the definition of fresh meat quality, meat quality traits and variations of meat quality. Also, this review presents recent knowledge underlying the relationship between fresh meat quality traits and muscle fiber characteristics. Finally, the present work proposes several potential factors including breed, genotype, sex, hormone, growth performance, diet, muscle location, exercise and ambient temperature that can be used to manipulate muscle fiber characteristics and subsequently meat quality in animals.
•Fresh meat qualities are affected by various intrinsic and extrinsic factors.•The meat quality is basically dependent on muscle fiber characteristics.•The meat quality can be improved by manipulation of muscle fiber characteristics.•Muscle fiber characteristics can be controlled by various potential factors.
Exercise is an effective intervention for the prevention and treatment of type 2 diabetes. Skeletal muscle combines multiple signals that contribute to the beneficial effects of exercise on ...cardiometabolic health. Inorganic nitrate increases exercise efficiency, tolerance, and performance. The transcriptional regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) coordinates the exercise-stimulated skeletal muscle fiber-type switch from glycolytic fast-twitch (type IIb) to oxidative slow-twitch (type I) and intermediate (type IIa) fibers, an effect reversed in insulin resistance and diabetes. We found that nitrate induces PGC1α expression and a switch toward type I and IIa fibers in rat muscle and myotubes in vitro. Nitrate induces the release of exercise/PGC1α-dependent myokine FNDC5/irisin and β-aminoisobutyric acid from myotubes and muscle in rats and humans. Both exercise and nitrate stimulated PGC1α-mediated γ-aminobutyric acid (GABA) secretion from muscle. Circulating GABA concentrations were increased in exercising mice and nitrate-treated rats and humans; thus, GABA may function as an exercise/PGC1α-mediated myokine-like small molecule. Moreover, nitrate increased circulating growth hormone levels in humans and rodents. Nitrate induces physiological responses that mimic exercise training and may underlie the beneficial effects of this metabolite on exercise and cardiometabolic health.
The variability of fiber type distribution in nine limb muscles was examined with histochemical and tensiomyographical (TMG) methods in two groups of 15 men aged between 17 and 40 years. The aim of ...this study was to determine the extent to which the relative occurrence of different fiber types and subtypes varies within human limb muscles in function to depth and to predict fiber type proportions with a non-invasive TMG method. The distribution of different fiber types varied within the muscles, as a function of depth, with a predominance of type 2b fibers at the surface and type 1 fibers in deeper regions of the muscle. For all the analyzed muscles the contraction times measured at stimulus intensity 10% of supramaximal stimulus (10% MS) were significantly (p<0.05) shorter than the contraction times measured at 50% of supramaximal stimulus intensity (50% MS). The Pearson's correlation coefficient between percentage of type 1 muscle fibers measured at the surface of the muscle and contraction time at 10% MS, obtained by TMG was statistically significant (r=0.76,P<0.01). Also the Pearson's correlation coefficient between percentage of type 1 muscle fibers measured in the deep region of the muscle and contraction time at 50% MS obtained by TMG was also statistically significant (r=0.90,P<0.001). These findings suggest that the contraction time obtained by TMG may be useful for non-invasive examining of muscle fiber types spatial distribution in humans.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that are widely involved in a variety of biological processes. Different skeletal muscle fiber type composition exhibits characteristic ...differences in functional properties and energy metabolism of skeletal muscle. However, the molecular mechanism by which miRNAs control the different type of muscle fiber formation is still not fully understood. In the present study, we characterized the role of microRNA-139-5p (miR-139-5p) in the regulation of myosin heavy chain (MyHC) isoform expression and its underlying mechanisms. Here we found that the expression of miR-139-5p was significantly higher in mouse slow-twitch muscle than in fast-twitch muscle. Overexpression of miR-139-5p downregulated the expression of MyHC I and MyHC IIa, whereas inhibition of miR-139-5p upregulated them. We also found that the levels of calcineurin (CaN), NFATc1, MEF2C and MCIP1.4, which are the components of CaN/NFAT signaling pathway that has shown to positively regulate slow fiber-selective gene expression, were notably inhibited by miR-139-5p overexpression. Furthermore, treatment of phenylephrine (PE), a α1-adrenoceptor agonist, abolished the inhibitory effect of miR-139-5p on MyHC I and MyHC IIa expression. Together, our findings indicated that the role of miR-139-5p in regulating the MyHC isoforms, especially MyHC I and MyHC IIa, may be achieved through inhibiting CaN/NFAT signaling pathway.
•MiR-139-5p was higher in mouse slow-twitch than in fast-twitch muscle.•MiR-139-5p overexpression downregulated the expression of MyHC I and MyHC IIa.•CaN/NFAT signaling was notably inhibited by miR-139-5p overexpression.•MiR-139-5p suppressed MyHC I and IIa expression via inhibiting CaN/NFAT signaling.
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