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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.

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Maximum rate of oxygen consumption (VO2max in nmol mm−3 s−1) of muscle preparations at physiological temperature from various species plotted against the cross-sectional area (in μm2) of the muscle cells in the preparation. A hyperbola was fitted through all data points. The fit hardly deviates from the Hill-type diffusion model shown in the text and is described by the function VO2max = constant CSA−1. The value of the constant is calculated as the mean of the products VO2max and CSA for each muscle fiber type and approximates 0.4 pmol mm−1 s−1. Inset cross sections stained for succinate dehydrogenase activity. From left to right: right ventricular wall of normal rat myocardium, rat extensor digitorum longus muscle, human vastus lateralis muscle, iliofibularis muscle of Xenopus laevis; scale bar 100 μm. ratMCT right ventricular rat cardiomyocytes of a monocrotaline-induced pulmonary hypertensive rat, humanCHF vastus lateralis muscle of human chronic heart failure patients. Figure adapted from (Bekedam et al. 2003; Van Der Laarse et al. 1998)
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Fig1: Maximum rate of oxygen consumption (VO2max in nmol mm−3 s−1) of muscle preparations at physiological temperature from various species plotted against the cross-sectional area (in μm2) of the muscle cells in the preparation. A hyperbola was fitted through all data points. The fit hardly deviates from the Hill-type diffusion model shown in the text and is described by the function VO2max = constant CSA−1. The value of the constant is calculated as the mean of the products VO2max and CSA for each muscle fiber type and approximates 0.4 pmol mm−1 s−1. Inset cross sections stained for succinate dehydrogenase activity. From left to right: right ventricular wall of normal rat myocardium, rat extensor digitorum longus muscle, human vastus lateralis muscle, iliofibularis muscle of Xenopus laevis; scale bar 100 μm. ratMCT right ventricular rat cardiomyocytes of a monocrotaline-induced pulmonary hypertensive rat, humanCHF vastus lateralis muscle of human chronic heart failure patients. Figure adapted from (Bekedam et al. 2003; Van Der Laarse et al. 1998)

Mentions: The maximum rates of oxygen consumption (VO2max) per volume unit and the cross-sectional areas of striated myocytes from different vertebrates vary over a 100-fold range. Muscle fibers with a high oxidative capacity are relatively small compared to fibers with a low oxidative capacity (Van Der Laarse et al. 1998), pointing to an inverse relationship between fiber cross-sectional area and VO2max (Fig. 1). A Hill-type model for oxygen diffusion (Hill 1965) predicts that the maximum value of the product, cross-sectional area × oxygen consumption, is limited by the extracellular oxygen tension as given by:\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\text{CSA}}\; V{\text{O}}_{{2{ \max }}} \le 4\pi \;\alpha_{\text{M}} D{\text{O}}_{2} \;P{\text{O}}_{2}, $$\end{document}where VO2max is the maximum rate of oxygen consumption in (nmol mm−3 s−1), CSA is the cross-sectional area of the myocyte (in mm2), αM is the solubility of oxygen in muscle (in mM mmHg−1), DO2 is the diffusion coefficient for oxygen in sarcoplasm (in mm2 s−1), and PO2 (in mmHg) equals the interstitial oxygen tension. If the value of the left-hand term of the equation is larger than that of the right-hand term, an anoxic core in the muscle cell will develop when the cell is maximally activated, causing a reduction in the rate of oxidative ATP production. Thus, any increase in either CSA or VO2max (or both) would require a proportional increase in extracellular PO2 above the value at which the core of the cell becomes anoxic at the maximum rate of oxygen consumption (PO2crit). Experimental determination of αM × DO2 (Krogh’s diffusion coefficient) at VO2max (van der Laarse et al. 2005) validated the Hill model and allowed estimating that striated muscle cells are evolved to function at their maximum rate of oxygen consumption at an extracellular PO2 of about 14 mmHg.Fig. 1


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)

Maximum rate of oxygen consumption (VO2max in nmol mm−3 s−1) of muscle preparations at physiological temperature from various species plotted against the cross-sectional area (in μm2) of the muscle cells in the preparation. A hyperbola was fitted through all data points. The fit hardly deviates from the Hill-type diffusion model shown in the text and is described by the function VO2max = constant CSA−1. The value of the constant is calculated as the mean of the products VO2max and CSA for each muscle fiber type and approximates 0.4 pmol mm−1 s−1. Inset cross sections stained for succinate dehydrogenase activity. From left to right: right ventricular wall of normal rat myocardium, rat extensor digitorum longus muscle, human vastus lateralis muscle, iliofibularis muscle of Xenopus laevis; scale bar 100 μm. ratMCT right ventricular rat cardiomyocytes of a monocrotaline-induced pulmonary hypertensive rat, humanCHF vastus lateralis muscle of human chronic heart failure patients. Figure adapted from (Bekedam et al. 2003; Van Der Laarse et al. 1998)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2957584&req=5

Fig1: Maximum rate of oxygen consumption (VO2max in nmol mm−3 s−1) of muscle preparations at physiological temperature from various species plotted against the cross-sectional area (in μm2) of the muscle cells in the preparation. A hyperbola was fitted through all data points. The fit hardly deviates from the Hill-type diffusion model shown in the text and is described by the function VO2max = constant CSA−1. The value of the constant is calculated as the mean of the products VO2max and CSA for each muscle fiber type and approximates 0.4 pmol mm−1 s−1. Inset cross sections stained for succinate dehydrogenase activity. From left to right: right ventricular wall of normal rat myocardium, rat extensor digitorum longus muscle, human vastus lateralis muscle, iliofibularis muscle of Xenopus laevis; scale bar 100 μm. ratMCT right ventricular rat cardiomyocytes of a monocrotaline-induced pulmonary hypertensive rat, humanCHF vastus lateralis muscle of human chronic heart failure patients. Figure adapted from (Bekedam et al. 2003; Van Der Laarse et al. 1998)
Mentions: The maximum rates of oxygen consumption (VO2max) per volume unit and the cross-sectional areas of striated myocytes from different vertebrates vary over a 100-fold range. Muscle fibers with a high oxidative capacity are relatively small compared to fibers with a low oxidative capacity (Van Der Laarse et al. 1998), pointing to an inverse relationship between fiber cross-sectional area and VO2max (Fig. 1). A Hill-type model for oxygen diffusion (Hill 1965) predicts that the maximum value of the product, cross-sectional area × oxygen consumption, is limited by the extracellular oxygen tension as given by:\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\text{CSA}}\; V{\text{O}}_{{2{ \max }}} \le 4\pi \;\alpha_{\text{M}} D{\text{O}}_{2} \;P{\text{O}}_{2}, $$\end{document}where VO2max is the maximum rate of oxygen consumption in (nmol mm−3 s−1), CSA is the cross-sectional area of the myocyte (in mm2), αM is the solubility of oxygen in muscle (in mM mmHg−1), DO2 is the diffusion coefficient for oxygen in sarcoplasm (in mm2 s−1), and PO2 (in mmHg) equals the interstitial oxygen tension. If the value of the left-hand term of the equation is larger than that of the right-hand term, an anoxic core in the muscle cell will develop when the cell is maximally activated, causing a reduction in the rate of oxidative ATP production. Thus, any increase in either CSA or VO2max (or both) would require a proportional increase in extracellular PO2 above the value at which the core of the cell becomes anoxic at the maximum rate of oxygen consumption (PO2crit). Experimental determination of αM × DO2 (Krogh’s diffusion coefficient) at VO2max (van der Laarse et al. 2005) validated the Hill model and allowed estimating that striated muscle cells are evolved to function at their maximum rate of oxygen consumption at an extracellular PO2 of about 14 mmHg.Fig. 1

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