Acute oral administration of L-leucine upregulates slow-fiber– and mitochondria-related genes in skeletal muscle of rats

2018 ◽  
Vol 57 ◽  
pp. 36-44 ◽  
Author(s):  
Yoriko Sato ◽  
Yusuke Sato ◽  
Kodwo Amuzuah Obeng ◽  
Fumiaki Yoshizawa
2005 ◽  
Vol 25 (15) ◽  
pp. 6629-6638 ◽  
Author(s):  
Misook Oh ◽  
Igor I. Rybkin ◽  
Victoria Copeland ◽  
Michael P. Czubryt ◽  
John M. Shelton ◽  
...  

ABSTRACT Skeletal muscles are a mosaic of slow and fast twitch myofibers. During embryogenesis, patterns of fiber type composition are initiated that change postnatally to meet physiological demand. To examine the role of the protein phosphatase calcineurin in the initiation and maintenance of muscle fiber types, we used a “Flox-ON” approach to obtain muscle-specific overexpression of the modulatory calcineurin-interacting protein 1 (MCIP1/DSCR1), an inhibitor of calcineurin. Myo-Cre transgenic mice with early skeletal muscle-specific expression of Cre recombinase were used to activate the Flox-MCIP1 transgene. Contractile components unique to type 1 slow fibers were absent from skeletal muscle of adult Myo-Cre/Flox-MCIP1 mice, whereas oxidative capacity, myoglobin content, and mitochondrial abundance were unaltered. The soleus muscles of Myo-Cre/Flox-MCIP1 mice fatigued more rapidly than the wild type as a consequence of the replacement of the slow myosin heavy chain MyHC-1 with a fast isoform, MyHC-2A. MyHC-1 expression in Myo-Cre/Flox-MCIP1 embryos and early neonates was normal. These results demonstrate that developmental patterning of slow fibers is independent of calcineurin, while the maintenance of the slow-fiber phenotype in the adult requires calcineurin activity.


2009 ◽  
Vol 297 (1) ◽  
pp. C6-C16 ◽  
Author(s):  
Clay E. Pandorf ◽  
Fadia Haddad ◽  
Carola Wright ◽  
Paul W. Bodell ◽  
Kenneth M. Baldwin

Recent advances in chromatin biology have enhanced our understanding of gene regulation. It is now widely appreciated that gene regulation is dependent upon post-translational modifications to the histones which package genes in the nucleus of cells. Active genes are known to be associated with acetylation of histones (H3ac) and trimethylation of lysine 4 in histone H3 (H3K4me3). Using chromatin immunoprecipitation (ChIP), we examined histone modifications at the myosin heavy chain (MHC) genes expressed in fast vs. slow fiber-type skeletal muscle, and in a model of muscle unloading, which results in a shift to fast MHC gene expression in slow muscles. Both H3ac and H3K4me3 varied directly with the transcriptional activity of the MHC genes in fast fiber-type plantaris and slow fiber-type soleus. During MHC transitions with muscle unloading, histone H3 at the type I MHC becomes de-acetylated in correspondence with down-regulation of that gene, while upregulation of the fast type IIx and IIb MHCs occurs in conjunction with enhanced H3ac in those MHCs. Enrichment of H3K4me3 is also increased at the type IIx and IIb MHCs when these genes are induced with muscle unloading. Downregulation of IIa MHC, however, was not associated with corresponding loss of H3ac or H3K4me3. These observations demonstrate the feasibility of using the ChIP assay to understand the native chromatin environment in adult skeletal muscle, and also suggest that the transcriptional state of types I, IIx and IIb MHC genes are sensitive to histone modifications both in different muscle fiber-types and in response to altered loading states.


2021 ◽  
Author(s):  
Byung-Hyun Park ◽  
Mi-Young Song ◽  
Chang Yeob Han ◽  
Young Jae Moon ◽  
Eun Ju Bae

Abstract Expanding the exercise capacity of skeletal muscle is an emerging strategy to combat obesity-related metabolic diseases and this can be achieved by shifting skeletal muscle fibers toward slow-twitch oxidative type. Here, we report that Sirt6, an anti-aging histone deacetylase, is critical in regulating myofiber configuration toward oxidative type and that Sirt6 activator can be an exercise mimetic. Genetic inactivation of Sirt6 in skeletal muscle reduced while its transgenic overexpression increased mitochondrial oxidative capacity and exercise performance in mice. Mechanistically, we show that Sirt6 downregulated Sox6, a key repressor of slow fiber specific gene, by increasing the transcription of CREB. Sirt6 expression is elevated in chronically exercised humans and mice treated with an activator of Sirt6 showed an increase in exercise endurance as compared to exercise-trained controls. Thus, the current study identifies Sirt6 as a new molecular target for reprogramming myofiber composition toward the oxidative type and for improving muscle performance.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 110-110
Author(s):  
Mao Ye ◽  
Zhiwen Song ◽  
Chenglong Jin ◽  
Chunqi Gao ◽  
Huichao Yan ◽  
...  

Abstract The type of myofiber is important for porcine meat quality. Meanwhile, the nt/Ca2+ pathway has been showed multiple roles in skeletal muscle formation; however, the distinct mechanism is still unclear. In this study, the weaned piglets and satellite cells were designed into the control group, lysine deficiency group and lysine rescue group to investigate the function of Wnt/Ca2+ pathway in governing skeletal muscle typing. After we confirm the growth of weaned piglets was controlled by lysine, the isobaric tag for relative and absolute quantification (iTRAQ) analysis of skeletal muscle detected that Wnt/Ca2+ pathway was involved in the transition of fast and slow fiber. Then, we found the ratio of type I myofiber in Semimembranous (fast muscle) was significantly increased after lysine deficiency (P < 0.05), and decreased by lysine rescue (P < 0.05). In contrast, the ratio of type I myofiber in Semitendinous muscle (slow muscle) was significantly decreased in the lysine deficiency group, and increased in the lysine rescue group (P < 0.05). Furthermore, the Wnt/Ca2+ pathway was significantly increased in Semimembranous muscle, while decreased in Semitendinous muscle with lysine deficiency, and this phenomenon was inversed after lysine rescue (P < 0.05). Meanwhile, the Wnt/Ca2+ pathway was stronger in satellite cells isolated from Semitendinous muscle (StSCs) than that of Semimembranous satellite cell (SmSCs) (P < 0.05). And we also found the StSCs enter in differentiation is more easily than SmSCs (P < 0.05). Besides, the ratio of type I myofiber originated from StSCs showed greater than StSCs (P < 0.05). In summary, we conclude that satellite cells participate in the Wnt/Ca2+ pathway controlled porcine myofiber determination.


2015 ◽  
Vol 34 ◽  
pp. S50-S51
Author(s):  
Y. Nishiyama ◽  
M. Miyoshi ◽  
M. Kai ◽  
M. Aoyama-Ishikawa ◽  
N. Maeshige ◽  
...  

1995 ◽  
Vol 78 (5) ◽  
pp. 1969-1976 ◽  
Author(s):  
D. L. Allen ◽  
S. R. Monke ◽  
R. J. Talmadge ◽  
R. R. Roy ◽  
V. R. Edgerton

Although a mammalian skeletal muscle fiber may contain thousands of myonuclei, the importance of this number or the potential to modulate it in adult muscle has not been clearly demonstrated. Using immunohistochemistry and confocal microscopy, we examined the plasticity of myonuclear number and fiber size in isolated fast and slow fiber segments from adult cat hindlimb muscles in response to chronic alterations in neuromuscular activity and loading. Compared with slow fibers in the soleus of control cats, myonuclear number in presumably transformed fast fibers was 32% lower and fiber size was decreased 73% after elimination of neuromuscular activation for 6 mo by spinal isolation. Slow fibers in the soleus of spinal-isolated cats had smaller cross-sectional areas, whereas myonuclear number was not significantly different than that in the control cats. Myonuclear number in fast plantaris fibers was more than threefold higher and fiber size was 2.8-fold higher after 3 mo of functional overload compared with the plantaris of control cats. Compared with control slow plantaris fibers, myonuclear number and fiber size also increased in overloaded slow plantaris fibers. These results demonstrate that changes in myonuclear number are associated with changes in myosin type and suggest that modulations in the amount of available DNA may be a factor in regulating cytoplasmic volume of muscle fibers in response to chronic changes in neuromuscular activity.


Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 869 ◽  
Author(s):  
Ohno ◽  
Ando ◽  
Ito ◽  
Suda ◽  
Matsui ◽  
...  

The effects of lactate on muscle mass and regeneration were investigated using mouse skeletal muscle tissue and cultured C2C12 cells. Male C57BL/6J mice were randomly divided into (1) control, (2) lactate (1 mol/L in distilled water, 8.9 mL/g body weight)-administered, (3) cardio toxin (CTX)-injected (CX), and (4) lactate-administered after CTX-injection (LX) groups. CTX was injected into right tibialis anterior (TA) muscle before the oral administration of sodium lactate (five days/week for two weeks) to the mice. Oral lactate administration increased the muscle weight and fiber cross-sectional area, and the population of Pax7-positive nuclei in mouse TA skeletal muscle. Oral administration of lactate also facilitated the recovery process of CTX-associated injured mouse TA muscle mass accompanied with a transient increase in the population of Pax7-positive nuclei. Mouse myoblast-derived C2C12 cells were differentiated for five days to form myotubes with or without lactate administration. C2C12 myotube formation with an increase in protein content, fiber diameter, length, and myo-nuclei was stimulated by lactate. These observations suggest that lactate may be a potential molecule to stimulate muscle hypertrophy and regeneration of mouse skeletal muscle via the activation of muscle satellite cells.


2012 ◽  
Vol 287 (42) ◽  
pp. 35351-35359 ◽  
Author(s):  
Douglas M. Anderson ◽  
Rajani George ◽  
Marcus B. Noyes ◽  
Megan Rowton ◽  
Wenjin Liu ◽  
...  

The homeobox transcription factor Mohawk (Mkx) is a potent transcriptional repressor expressed in the embryonic precursors of skeletal muscle, cartilage, and bone. MKX has recently been shown to be a critical regulator of musculoskeletal tissue differentiation and gene expression; however, the genetic pathways through which MKX functions and its DNA-binding properties are currently unknown. Using a modified bacterial one-hybrid site selection assay, we determined the core DNA-recognition motif of the mouse monomeric Mkx homeodomain to be A-C-A. Using cell-based assays, we have identified a minimal Mkx-responsive element (MRE) located within the Mkx promoter, which is composed of a highly conserved inverted repeat of the core Mkx recognition motif. Using the minimal MRE sequence, we have further identified conserved MREs within the locus of Sox6, a transcription factor that represses slow fiber gene expression during skeletal muscle differentiation. Real-time PCR and immunostaining of in vitro differentiated muscle satellite cells isolated from Mkx-null mice revealed an increase in the expression of Sox6 and down-regulation of slow fiber structural genes. Together, these data identify the unique DNA-recognition properties of MKX and reveal a novel role for Mkx in promoting slow fiber type specification during skeletal muscle differentiation.


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