Limits...
The muscle fiber type-fiber size paradox: hypertrophy or oxidative metabolism?

van Wessel T, de Haan A, van der Laarse WJ, Jaspers RT - Eur. J. Appl. Physiol. (2010)

Bottom Line: New experimental data and an inventory of critical stimuli and state of activation of the signaling pathways involved in regulating contractile and metabolic protein turnover reveal: (1) higher capacity for protein synthesis in high compared to low oxidative fibers; (2) competition between signaling pathways for synthesis of myofibrillar proteins and proteins associated with oxidative metabolism; i.e., increased mitochondrial biogenesis via AMP-activated protein kinase attenuates the rate of protein synthesis; (3) relatively higher expression levels of E3-ligases and proteasome-mediated protein degradation in high oxidative fibers.Therefore, one needs to know the relative contribution of the signaling pathways to protein turnover in high and low oxidative fibers.The outcome and ideas presented are relevant to optimizing treatment and training in the fields of sports, cardiology, oncology, pulmonology and rehabilitation medicine.

View Article: PubMed Central - PubMed

Affiliation: Research Institute MOVE, Faculty of Human Movement Sciences, VU University Amsterdam, Van der Boechorststraat 9, 1081 BT, Amsterdam, The Netherlands.

ABSTRACT
An inverse relationship exists between striated muscle fiber size and its oxidative capacity. This relationship implies that muscle fibers, which are triggered to simultaneously increase their mass/strength (hypertrophy) and fatigue resistance (oxidative capacity), increase these properties (strength or fatigue resistance) to a lesser extent compared to fibers increasing either of these alone. Muscle fiber size and oxidative capacity are determined by the balance between myofibrillar protein synthesis, mitochondrial biosynthesis and degradation. New experimental data and an inventory of critical stimuli and state of activation of the signaling pathways involved in regulating contractile and metabolic protein turnover reveal: (1) higher capacity for protein synthesis in high compared to low oxidative fibers; (2) competition between signaling pathways for synthesis of myofibrillar proteins and proteins associated with oxidative metabolism; i.e., increased mitochondrial biogenesis via AMP-activated protein kinase attenuates the rate of protein synthesis; (3) relatively higher expression levels of E3-ligases and proteasome-mediated protein degradation in high oxidative fibers. These observations could explain the fiber type-fiber size paradox that despite the high capacity for protein synthesis in high oxidative fibers, these fibers remain relatively small. However, it remains challenging to understand the mechanisms by which contractile activity, mechanical loading, cellular energy status and cellular oxygen tension affect regulation of fiber size. Therefore, one needs to know the relative contribution of the signaling pathways to protein turnover in high and low oxidative fibers. The outcome and ideas presented are relevant to optimizing treatment and training in the fields of sports, cardiology, oncology, pulmonology and rehabilitation medicine.

Show MeSH

Related in: MedlinePlus

Differences in mRNA concentrations of glyceralde-3 phosphate dehydrogenase (GAPDH), 18S RNA, α-skeletal actin (α-sk actin), muscle ring finger-1 (MuRF1) and muscle atrophy F-box (MAFbx) in high oxidative rat soleus (SO) and low oxidative extensor digitorum longus (EDL) muscles (n = 6) (for methods see supplementary section I). a Total RNA (μg) normalized to muscle tissue weight (mg) showed that SO contains 2.3-fold more total RNA per milligram muscle tissue compared to EDL (p < 0.001). b mRNA normalized to total RNA relative to EDL. No differences between SO and EDL were found for any marker, except for GAPDH that showed 2.7-fold lower expression in SO (p < 0.001). c mRNA normalized to muscle tissue weight relative to EDL. GAPDH showed no significant difference between SO and EDL, whereas 18S RNA (2.1-fold), α-sk actin (2.3-fold), MuRF1 (2.1-fold) and MAFbx (1.8-fold) were all higher in SO (p < 0.05). Asterisks indicate significant difference compared to EDL. Systematic comparison of oxidative capacity and fiber cross-sectional area (CSA) from various hind limb muscles in the rat (Armstrong and Phelps 1984) show that SO predominantly (~90%) consists of slow contracting fibers with high oxidative capacity, whereas EDL contains largely (~60%) fast contracting glycolytic fibers with the lowest oxidative capacity. Within EDL, the high oxidative fibers show significantly smaller CSA than low oxidative fibers and also high oxidative fibers in SO show smaller CSA compared to the low oxidative fibers in EDL (Armstrong and Phelps 1984; Nakatani et al. 1999). Based on these observations and the data from Figs. 1 and 2, it can be concluded that high oxidative fibers are generally smaller and also contain more 18S RNA, α-sk actin-, MuRF1- and MAFbx-mRNA, compared to low oxidative fibers. The literature on rat SO and EDL fiber type composition does not unambiguously show that high oxidative fibers have smaller CSA compared to low oxidative fibers (Deveci et al. 2001; Kupa et al. 1995; Torrejais et al. 1999). The inconsistencies in CSA data of the latter studies compared to other studies with a more systematic approach (Armstrong and Phelps 1984; Nakatani et al. 1999) may be related to age, gender, muscle region or the effect of treatment. In addition, the differences in CSA between high and low oxidative fibers were not always tested for statistical significance. This impairs comparison of these studies, largely because classification of the muscle fiber type highly depends on the reaction intensity of the staining in different fiber cross sections and therefore may yield considerable variation in the estimation of fiber populations
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2957584&req=5

Fig2: Differences in mRNA concentrations of glyceralde-3 phosphate dehydrogenase (GAPDH), 18S RNA, α-skeletal actin (α-sk actin), muscle ring finger-1 (MuRF1) and muscle atrophy F-box (MAFbx) in high oxidative rat soleus (SO) and low oxidative extensor digitorum longus (EDL) muscles (n = 6) (for methods see supplementary section I). a Total RNA (μg) normalized to muscle tissue weight (mg) showed that SO contains 2.3-fold more total RNA per milligram muscle tissue compared to EDL (p < 0.001). b mRNA normalized to total RNA relative to EDL. No differences between SO and EDL were found for any marker, except for GAPDH that showed 2.7-fold lower expression in SO (p < 0.001). c mRNA normalized to muscle tissue weight relative to EDL. GAPDH showed no significant difference between SO and EDL, whereas 18S RNA (2.1-fold), α-sk actin (2.3-fold), MuRF1 (2.1-fold) and MAFbx (1.8-fold) were all higher in SO (p < 0.05). Asterisks indicate significant difference compared to EDL. Systematic comparison of oxidative capacity and fiber cross-sectional area (CSA) from various hind limb muscles in the rat (Armstrong and Phelps 1984) show that SO predominantly (~90%) consists of slow contracting fibers with high oxidative capacity, whereas EDL contains largely (~60%) fast contracting glycolytic fibers with the lowest oxidative capacity. Within EDL, the high oxidative fibers show significantly smaller CSA than low oxidative fibers and also high oxidative fibers in SO show smaller CSA compared to the low oxidative fibers in EDL (Armstrong and Phelps 1984; Nakatani et al. 1999). Based on these observations and the data from Figs. 1 and 2, it can be concluded that high oxidative fibers are generally smaller and also contain more 18S RNA, α-sk actin-, MuRF1- and MAFbx-mRNA, compared to low oxidative fibers. The literature on rat SO and EDL fiber type composition does not unambiguously show that high oxidative fibers have smaller CSA compared to low oxidative fibers (Deveci et al. 2001; Kupa et al. 1995; Torrejais et al. 1999). The inconsistencies in CSA data of the latter studies compared to other studies with a more systematic approach (Armstrong and Phelps 1984; Nakatani et al. 1999) may be related to age, gender, muscle region or the effect of treatment. In addition, the differences in CSA between high and low oxidative fibers were not always tested for statistical significance. This impairs comparison of these studies, largely because classification of the muscle fiber type highly depends on the reaction intensity of the staining in different fiber cross sections and therefore may yield considerable variation in the estimation of fiber populations

Mentions: Quantifying mRNA levels of structural muscle protein in different fiber types requires accurate normalization, which is usually done relative to housekeeping genes necessary for basic cellular function (e.g., β-actin, GAPDH and 18S rRNA). Apparently, expression levels of these housekeeping genes can vary depending on the experimental model, species, pathological condition (e.g., Bas et al. 2004; Plomgaard et al. 2006) and the type of muscle (Fig. 2; see supplementary section I for methods). To our knowledge, very little comparative data are available regarding gene transcription in high and low oxidative muscle fibers. Using in situ hybridizations, it has been shown in rat muscle fibers that the amount of MyHC mRNA per microgram total RNA did not differ between fiber types (Habets et al. 1999). However, the total RNA content in high oxidative type I fibers was twofold higher compared to IIA fibers and five- to sixfold higher than IIB fibers with the lowest oxidative capacity. As a consequence, the MyHC mRNA content was substantially higher in high compared to low oxidative fibers. Thus far, fiber type-specific α-skeletal actin levels have not been reported. Using a quantitative PCR technique, we have quantified that predominantly high and low oxidative muscles contain different levels of 18S rRNA and α-skeletal actin mRNA (Fig. 2). Total RNA per microgram muscle tissue is 2.3-fold higher in the high oxidative soleus compared to the low oxidative EDL (Fig. 2a). The fraction of 18S rRNA and α-skeletal actin mRNA on the total RNA is similar in both muscles (Fig. 2b). However, taking into account normalization per microgram muscle tissue, the 18S rRNA and α-actin mRNA levels are 2.1 and 2.3-fold higher, respectively, in soleus compared to EDL (Fig. 2c). Within Xenopus iliofibularis muscles, we found positive correlations (r2 = 0.71 and r2 = 0.54, p < 0.0001) between mitochondrial density and α-actin expression (Suppl. Fig. 1, see supplementary section II for methods), which also indicates that within a muscle high oxidative muscle fibers contain higher α-actin expression compared to low oxidative fibers.Fig. 2


The muscle fiber type-fiber size paradox: hypertrophy or oxidative metabolism?

van Wessel T, de Haan A, van der Laarse WJ, Jaspers RT - Eur. J. Appl. Physiol. (2010)

Differences in mRNA concentrations of glyceralde-3 phosphate dehydrogenase (GAPDH), 18S RNA, α-skeletal actin (α-sk actin), muscle ring finger-1 (MuRF1) and muscle atrophy F-box (MAFbx) in high oxidative rat soleus (SO) and low oxidative extensor digitorum longus (EDL) muscles (n = 6) (for methods see supplementary section I). a Total RNA (μg) normalized to muscle tissue weight (mg) showed that SO contains 2.3-fold more total RNA per milligram muscle tissue compared to EDL (p < 0.001). b mRNA normalized to total RNA relative to EDL. No differences between SO and EDL were found for any marker, except for GAPDH that showed 2.7-fold lower expression in SO (p < 0.001). c mRNA normalized to muscle tissue weight relative to EDL. GAPDH showed no significant difference between SO and EDL, whereas 18S RNA (2.1-fold), α-sk actin (2.3-fold), MuRF1 (2.1-fold) and MAFbx (1.8-fold) were all higher in SO (p < 0.05). Asterisks indicate significant difference compared to EDL. Systematic comparison of oxidative capacity and fiber cross-sectional area (CSA) from various hind limb muscles in the rat (Armstrong and Phelps 1984) show that SO predominantly (~90%) consists of slow contracting fibers with high oxidative capacity, whereas EDL contains largely (~60%) fast contracting glycolytic fibers with the lowest oxidative capacity. Within EDL, the high oxidative fibers show significantly smaller CSA than low oxidative fibers and also high oxidative fibers in SO show smaller CSA compared to the low oxidative fibers in EDL (Armstrong and Phelps 1984; Nakatani et al. 1999). Based on these observations and the data from Figs. 1 and 2, it can be concluded that high oxidative fibers are generally smaller and also contain more 18S RNA, α-sk actin-, MuRF1- and MAFbx-mRNA, compared to low oxidative fibers. The literature on rat SO and EDL fiber type composition does not unambiguously show that high oxidative fibers have smaller CSA compared to low oxidative fibers (Deveci et al. 2001; Kupa et al. 1995; Torrejais et al. 1999). The inconsistencies in CSA data of the latter studies compared to other studies with a more systematic approach (Armstrong and Phelps 1984; Nakatani et al. 1999) may be related to age, gender, muscle region or the effect of treatment. In addition, the differences in CSA between high and low oxidative fibers were not always tested for statistical significance. This impairs comparison of these studies, largely because classification of the muscle fiber type highly depends on the reaction intensity of the staining in different fiber cross sections and therefore may yield considerable variation in the estimation of fiber populations
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957584&req=5

Fig2: Differences in mRNA concentrations of glyceralde-3 phosphate dehydrogenase (GAPDH), 18S RNA, α-skeletal actin (α-sk actin), muscle ring finger-1 (MuRF1) and muscle atrophy F-box (MAFbx) in high oxidative rat soleus (SO) and low oxidative extensor digitorum longus (EDL) muscles (n = 6) (for methods see supplementary section I). a Total RNA (μg) normalized to muscle tissue weight (mg) showed that SO contains 2.3-fold more total RNA per milligram muscle tissue compared to EDL (p < 0.001). b mRNA normalized to total RNA relative to EDL. No differences between SO and EDL were found for any marker, except for GAPDH that showed 2.7-fold lower expression in SO (p < 0.001). c mRNA normalized to muscle tissue weight relative to EDL. GAPDH showed no significant difference between SO and EDL, whereas 18S RNA (2.1-fold), α-sk actin (2.3-fold), MuRF1 (2.1-fold) and MAFbx (1.8-fold) were all higher in SO (p < 0.05). Asterisks indicate significant difference compared to EDL. Systematic comparison of oxidative capacity and fiber cross-sectional area (CSA) from various hind limb muscles in the rat (Armstrong and Phelps 1984) show that SO predominantly (~90%) consists of slow contracting fibers with high oxidative capacity, whereas EDL contains largely (~60%) fast contracting glycolytic fibers with the lowest oxidative capacity. Within EDL, the high oxidative fibers show significantly smaller CSA than low oxidative fibers and also high oxidative fibers in SO show smaller CSA compared to the low oxidative fibers in EDL (Armstrong and Phelps 1984; Nakatani et al. 1999). Based on these observations and the data from Figs. 1 and 2, it can be concluded that high oxidative fibers are generally smaller and also contain more 18S RNA, α-sk actin-, MuRF1- and MAFbx-mRNA, compared to low oxidative fibers. The literature on rat SO and EDL fiber type composition does not unambiguously show that high oxidative fibers have smaller CSA compared to low oxidative fibers (Deveci et al. 2001; Kupa et al. 1995; Torrejais et al. 1999). The inconsistencies in CSA data of the latter studies compared to other studies with a more systematic approach (Armstrong and Phelps 1984; Nakatani et al. 1999) may be related to age, gender, muscle region or the effect of treatment. In addition, the differences in CSA between high and low oxidative fibers were not always tested for statistical significance. This impairs comparison of these studies, largely because classification of the muscle fiber type highly depends on the reaction intensity of the staining in different fiber cross sections and therefore may yield considerable variation in the estimation of fiber populations
Mentions: Quantifying mRNA levels of structural muscle protein in different fiber types requires accurate normalization, which is usually done relative to housekeeping genes necessary for basic cellular function (e.g., β-actin, GAPDH and 18S rRNA). Apparently, expression levels of these housekeeping genes can vary depending on the experimental model, species, pathological condition (e.g., Bas et al. 2004; Plomgaard et al. 2006) and the type of muscle (Fig. 2; see supplementary section I for methods). To our knowledge, very little comparative data are available regarding gene transcription in high and low oxidative muscle fibers. Using in situ hybridizations, it has been shown in rat muscle fibers that the amount of MyHC mRNA per microgram total RNA did not differ between fiber types (Habets et al. 1999). However, the total RNA content in high oxidative type I fibers was twofold higher compared to IIA fibers and five- to sixfold higher than IIB fibers with the lowest oxidative capacity. As a consequence, the MyHC mRNA content was substantially higher in high compared to low oxidative fibers. Thus far, fiber type-specific α-skeletal actin levels have not been reported. Using a quantitative PCR technique, we have quantified that predominantly high and low oxidative muscles contain different levels of 18S rRNA and α-skeletal actin mRNA (Fig. 2). Total RNA per microgram muscle tissue is 2.3-fold higher in the high oxidative soleus compared to the low oxidative EDL (Fig. 2a). The fraction of 18S rRNA and α-skeletal actin mRNA on the total RNA is similar in both muscles (Fig. 2b). However, taking into account normalization per microgram muscle tissue, the 18S rRNA and α-actin mRNA levels are 2.1 and 2.3-fold higher, respectively, in soleus compared to EDL (Fig. 2c). Within Xenopus iliofibularis muscles, we found positive correlations (r2 = 0.71 and r2 = 0.54, p < 0.0001) between mitochondrial density and α-actin expression (Suppl. Fig. 1, see supplementary section II for methods), which also indicates that within a muscle high oxidative muscle fibers contain higher α-actin expression compared to low oxidative fibers.Fig. 2

Bottom Line: New experimental data and an inventory of critical stimuli and state of activation of the signaling pathways involved in regulating contractile and metabolic protein turnover reveal: (1) higher capacity for protein synthesis in high compared to low oxidative fibers; (2) competition between signaling pathways for synthesis of myofibrillar proteins and proteins associated with oxidative metabolism; i.e., increased mitochondrial biogenesis via AMP-activated protein kinase attenuates the rate of protein synthesis; (3) relatively higher expression levels of E3-ligases and proteasome-mediated protein degradation in high oxidative fibers.Therefore, one needs to know the relative contribution of the signaling pathways to protein turnover in high and low oxidative fibers.The outcome and ideas presented are relevant to optimizing treatment and training in the fields of sports, cardiology, oncology, pulmonology and rehabilitation medicine.

View Article: PubMed Central - PubMed

Affiliation: Research Institute MOVE, Faculty of Human Movement Sciences, VU University Amsterdam, Van der Boechorststraat 9, 1081 BT, Amsterdam, The Netherlands.

ABSTRACT
An inverse relationship exists between striated muscle fiber size and its oxidative capacity. This relationship implies that muscle fibers, which are triggered to simultaneously increase their mass/strength (hypertrophy) and fatigue resistance (oxidative capacity), increase these properties (strength or fatigue resistance) to a lesser extent compared to fibers increasing either of these alone. Muscle fiber size and oxidative capacity are determined by the balance between myofibrillar protein synthesis, mitochondrial biosynthesis and degradation. New experimental data and an inventory of critical stimuli and state of activation of the signaling pathways involved in regulating contractile and metabolic protein turnover reveal: (1) higher capacity for protein synthesis in high compared to low oxidative fibers; (2) competition between signaling pathways for synthesis of myofibrillar proteins and proteins associated with oxidative metabolism; i.e., increased mitochondrial biogenesis via AMP-activated protein kinase attenuates the rate of protein synthesis; (3) relatively higher expression levels of E3-ligases and proteasome-mediated protein degradation in high oxidative fibers. These observations could explain the fiber type-fiber size paradox that despite the high capacity for protein synthesis in high oxidative fibers, these fibers remain relatively small. However, it remains challenging to understand the mechanisms by which contractile activity, mechanical loading, cellular energy status and cellular oxygen tension affect regulation of fiber size. Therefore, one needs to know the relative contribution of the signaling pathways to protein turnover in high and low oxidative fibers. The outcome and ideas presented are relevant to optimizing treatment and training in the fields of sports, cardiology, oncology, pulmonology and rehabilitation medicine.

Show MeSH
Related in: MedlinePlus