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Changes in skeletal muscle fiber types induced by chronic kidney disease
letter to the editor
Changes in skeletal muscle fiber types induced by chronic kidney disease To the Editor: In a recent interesting study on a mouse model of chronic kidney disease (CKD), Tamaki et al.1 reported that CKD causes a decrease in the proportion of type I (slow oxidative) and IIA (fast oxidative glycolytic) and a relative increase in IIB (fast glycolytic) muscle fibers, using succinate dehydrogenase (SDH) activity for fiber typing. This result is surprising as a change in the opposite direction, with an increase in type I and a decrease in IIX fibers, was observed in chronic hemodialysis patients using myosin immunohistochemistry for fiber typing.2 This discrepancy could be due to the different species or stage of kidney disease, but might also reflect the different fiber typing procedure. Type I and mitochondria-rich type IIA and IIX fibers can be identified by myosin ATPase activity or isoform-specific antimyosin antibodies, but not by SDH staining. Indeed, contrary to the frequent assumption that type I fibers have the highest SDH activity levels, actually IIA and many IIX fibers have a higher SDH activity than type I fibers in mouse and rat muscles (Figure 1).3 Furthermore, in the specific CKD context, SDH activity is probably affected by the mitochondrial dysfunction itself and was in fact decreased in hemodialysis patients.2 One may wonder whether the mitochondrial changes described in the mouse model involve all muscle fibers or affect differentially the various fiber types. This question is especially interesting in view of the mitochondrial specialization revealed by single muscle fiber proteomics.4
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Figure 1 | Fiber types in mouse skeletal muscle identified by succinate dehydrogenase (SDH) enzyme histochemistry and myosin immunohistochemistry. Serial sections of mouse soleus muscle were stained for myosin isoforms (left panel) or SDH activity (right panel). Myosin isoforms were identified with antibodies specific for type I (blue) and IIA (green) myosin heavy chains, whereas type IIX fibers are unstained and appear black. Note that type IIA (*) and IIX (x) fibers stain more intensely for SDH activity than type I fibers ( ). The same is true for mouse fast muscles, except that type IIX fibers show variable SDH activity in these muscles. Scale bar = 50 μm.
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Tamaki M, Miyashita K, Wakino S et al. Chronic kidney disease reduces muscle mitochondria and exercise endurance and its exacerbation by dietary protein through inactivation of pyruvate dehydrogenase. Kidney Int 2014; 85: 1330–1339. 2. Lewis MI, Fournier M, Wang H et al. Metabolic and morphometric profile of muscle fibers in chronic hemodialysis patients. J Appl Physiol 2012; 112: 72–78. 3. Schiaffino S. Fibre types in skeletal muscle: a personal account. Acta Physiol 2010; 199: 451–463. 4. Murgia M, Nagaraj N, Deshmukh A et al. Single muscle fiber proteomics reveals unexpected mitochondrial specialization. EMBO Rep 2015; 16: 387–395.
Stefano Schiaffino1 and Irene Moretti1 1
Venetian Institute of Molecular Medicine, Padova, Italy Correspondence: Stefano Schiaffino, Venetian Institute of Molecular Medicine, Via Orus 2, Padova 35129, Italy. E-mail: [email protected] Kidney International (2015) 88, 412; doi:10.1038/ki.2015.168
The Authors Reply: We greatly appreciate Drs Schiaffino and Moretti1 for the comments that pointed out the different results about muscle fiber type changes in chronic kidney disease (CKD) and remarked a pitfall of succinate dehydrogenase (SDH) staining. Our study showed a decrease in type I and IIa oxidative muscle fibers and an increase in type IIb fibers in the deep regions of the extensor digitorum longus (EDLd) muscle of 5/6 nephrectomized CKD model mice. On the other hand, they demonstrated a result that showed changes in opposite direction of the fiber type in the vastus lateralis muscle of hemodialysis patients. Several possibilities regarding this discrepancy can be postulated. We can speculate culprit substances for fiber type changes in CKD that are removable by hemodialysis. Hemodialysis might remove these substances and change fiber type toward opposite direction from CKD patients. Fiber type changes toward type I are provoked by various factors: exercise, weight loss, and aging.2 Hemodialysis might exacerbate aging phenotypes and promote fiber type changes toward type I, as is similar to the case of promotion of arteriosclerosis, a representative sign of aging, in hemodialysis patients.3 As you pointed out, SDH activity might be similar between type I and IIa fibers in the EDLd muscle of mice.4 More detailed observation by using myosin monoclonal antibody must be preferable. In previous reports, fiber type changes associated with CKD or dialysis have been controversial. Single muscle fiber proteomics, presented in the letter,1 will have a significant role to solve the conflict. 1. 2.
Schiaffino S, Moretti I. Changes in skeletal muscle fiber types induced by chronic kidney disease. Kidney Int 2015; 88: 412. Pette D, Staron RS. Mammalian skeletal muscle fiber type transitions. Int Rev Cytol 1997; 170: 143–223.
Kidney International (2015) 88, 412–414
Changes in skeletal muscle fiber types induced by chronic kidney disease To the Editor: In a recent interesting study on a mouse model of chronic kidney disease (CKD), Tamaki et al.1 reported that CKD causes a decrease in the proportion of type I (slow oxidative) and IIA (fast oxidative glycolytic) and a relative increase in IIB (fast glycolytic) muscle fibers, using succinate dehydrogenase (SDH) activity for fiber typing. This result is surprising as a change in the opposite direction, with an increase in type I and a decrease in IIX fibers, was observed in chronic hemodialysis patients using myosin immunohistochemistry for fiber typing.2 This discrepancy could be due to the different species or stage of kidney disease, but might also reflect the different fiber typing procedure. Type I and mitochondria-rich type IIA and IIX fibers can be identified by myosin ATPase activity or isoform-specific antimyosin antibodies, but not by SDH staining. Indeed, contrary to the frequent assumption that type I fibers have the highest SDH activity levels, actually IIA and many IIX fibers have a higher SDH activity than type I fibers in mouse and rat muscles (Figure 1).3 Furthermore, in the specific CKD context, SDH activity is probably affected by the mitochondrial dysfunction itself and was in fact decreased in hemodialysis patients.2 One may wonder whether the mitochondrial changes described in the mouse model involve all muscle fibers or affect differentially the various fiber types. This question is especially interesting in view of the mitochondrial specialization revealed by single muscle fiber proteomics.4
x
x
x
x
* *
*
*
x
*
*
x
Figure 1 | Fiber types in mouse skeletal muscle identified by succinate dehydrogenase (SDH) enzyme histochemistry and myosin immunohistochemistry. Serial sections of mouse soleus muscle were stained for myosin isoforms (left panel) or SDH activity (right panel). Myosin isoforms were identified with antibodies specific for type I (blue) and IIA (green) myosin heavy chains, whereas type IIX fibers are unstained and appear black. Note that type IIA (*) and IIX (x) fibers stain more intensely for SDH activity than type I fibers ( ). The same is true for mouse fast muscles, except that type IIX fibers show variable SDH activity in these muscles. Scale bar = 50 μm.
•
412
1.
Tamaki M, Miyashita K, Wakino S et al. Chronic kidney disease reduces muscle mitochondria and exercise endurance and its exacerbation by dietary protein through inactivation of pyruvate dehydrogenase. Kidney Int 2014; 85: 1330–1339. 2. Lewis MI, Fournier M, Wang H et al. Metabolic and morphometric profile of muscle fibers in chronic hemodialysis patients. J Appl Physiol 2012; 112: 72–78. 3. Schiaffino S. Fibre types in skeletal muscle: a personal account. Acta Physiol 2010; 199: 451–463. 4. Murgia M, Nagaraj N, Deshmukh A et al. Single muscle fiber proteomics reveals unexpected mitochondrial specialization. EMBO Rep 2015; 16: 387–395.
Stefano Schiaffino1 and Irene Moretti1 1
Venetian Institute of Molecular Medicine, Padova, Italy Correspondence: Stefano Schiaffino, Venetian Institute of Molecular Medicine, Via Orus 2, Padova 35129, Italy. E-mail: [email protected] Kidney International (2015) 88, 412; doi:10.1038/ki.2015.168
The Authors Reply: We greatly appreciate Drs Schiaffino and Moretti1 for the comments that pointed out the different results about muscle fiber type changes in chronic kidney disease (CKD) and remarked a pitfall of succinate dehydrogenase (SDH) staining. Our study showed a decrease in type I and IIa oxidative muscle fibers and an increase in type IIb fibers in the deep regions of the extensor digitorum longus (EDLd) muscle of 5/6 nephrectomized CKD model mice. On the other hand, they demonstrated a result that showed changes in opposite direction of the fiber type in the vastus lateralis muscle of hemodialysis patients. Several possibilities regarding this discrepancy can be postulated. We can speculate culprit substances for fiber type changes in CKD that are removable by hemodialysis. Hemodialysis might remove these substances and change fiber type toward opposite direction from CKD patients. Fiber type changes toward type I are provoked by various factors: exercise, weight loss, and aging.2 Hemodialysis might exacerbate aging phenotypes and promote fiber type changes toward type I, as is similar to the case of promotion of arteriosclerosis, a representative sign of aging, in hemodialysis patients.3 As you pointed out, SDH activity might be similar between type I and IIa fibers in the EDLd muscle of mice.4 More detailed observation by using myosin monoclonal antibody must be preferable. In previous reports, fiber type changes associated with CKD or dialysis have been controversial. Single muscle fiber proteomics, presented in the letter,1 will have a significant role to solve the conflict. 1. 2.
Schiaffino S, Moretti I. Changes in skeletal muscle fiber types induced by chronic kidney disease. Kidney Int 2015; 88: 412. Pette D, Staron RS. Mammalian skeletal muscle fiber type transitions. Int Rev Cytol 1997; 170: 143–223.
Kidney International (2015) 88, 412–414