Eicosapentaenoic acid increases proportion of type 1 muscle fibers through PPARδ and AMPK pathways in rats.

Muscle fiber type composition (% slow-twitch and % fast-twitch fibers) is associated with metabolism, with increased slow-twitch fibers alleviating metabolic disorders. Previously, we reported that dietary fish oil intake induced a muscle fiber-type transition in a slower direction in rats. The aim of this study was to determine the functionality of eicosapentaenoic acid (EPA), a unique fatty acid in fish oil, to skeletal muscle fiber type and metabolism in rats.

Dietary oleic acid intake increases the proportion of type 1 and 2X muscle fibers in mice.

Skeletal muscle is one of the largest metabolic tissues in mammals and is composed of four different types of muscle fibers (types 1, 2A, 2X, and 2B); however, type 2B is absent in humans. Given that slow-twitch fibers are superior to fast-twitch fibers in terms of oxidative metabolism and are rich in mitochondria, shift of muscle fiber types in direction towards slower fiber types improves metabolic disorders and endurance capacity. We previously had reported that oleic acid supplementation increases type 1 fiber formation in C2C12 myotubes; however, its function still remains unclear.

Age-related nitration/dysfunction of myogenic stem cell activator HGF.

Mechanical perturbation triggers activation of resident myogenic stem cells to enter the cell cycle through a cascade of events including hepatocyte growth factor (HGF) release from its extracellular tethering and the subsequent presentation to signaling-receptor c-met. Here, we show that with aging, extracellular HGF undergoes tyrosine-residue (Y) nitration and loses c-met binding, thereby disturbing muscle homeostasis. Biochemical studies demonstrated that nitration/dysfunction is specific to HGF among other major growth factors and is characterized by its locations at Y198 and Y250 in c-met-binding domains.

Netrin-4 synthesized in satellite cell-derived myoblasts stimulates autonomous fusion.

Satellite cells are indispensable for skeletal muscle regeneration and hypertrophy by forming nascent myofibers (myotubes). They synthesize multi-potent modulator netrins (secreted subtypes: netrin-1, -3, and -4), originally found as classical neural axon guidance molecules. While netrin-1 and -3 have key roles in myogenic differentiation, the physiological significance of netrin-4 is still unclear.

Up- and Downregulated Genes after Long-Term Muscle Atrophy Induced by Denervation in Mice Detected Using RNA-Seq.

Skeletal muscle atrophy occurs rapidly as a result of inactivity. Although there are many reports on changes in gene expression during the early phase of muscle atrophy, the patterns of up-and downregulated gene expression after long-term and equilibrated muscle atrophy are poorly understood. In this study, we comprehensively examined the changes in gene expression in long-term denervated mouse muscles using RNA-Seq.

Circulating α-Klotho Counteracts Transforming Growth Factor-β-Induced Sarcopenia.

α-Klotho is a longevity-related protein. Its deficiency shortens lifespan with prominent senescent phenotypes, including muscle atrophy and weakness in mice. α-Klotho has two forms: membrane α-Klotho and circulating α-Klotho (c-α-Klotho).

Connexin 43 is Localized in Gizzard Smooth Muscle Cells during Chicken Development.

Smooth muscle cells are widely distributed in the digestive organs of chickens. They exist as single cells, but adhere to each other to function synchronously. In this study, the expression of the gap junction protein connexin 43 (Cx43) in chicken gizzards was investigated at embryonic days (E) 10, E15, and E18.

A pilot study on nitration/dysfunction of NK1 segment of myogenic stem cell activator HGF.

Protein tyrosine residue (Y) nitration, a post-translational chemical-modification mode, has been associated with changes in protein activity and function; hence the accumulation of specific nitrated proteins in tissues may be used to monitor the onset and progression of pathological disorders. To verify the possible impact of nitration on postnatal muscle growth and regeneration, a pilot study was designed to examine the nitration/dysfunction of hepatocyte growth factor (HGF), a key ligand that is released from the extracellular tethering and activates myogenic stem satellite cells to enter the cell cycle upon muscle stretch and injury. Exposure of recombinant HGF (a hetero-dimer of α- and β-chains) to peroxynitrite induces Y nitration in HGF α-chain under physiological conditions.

Abundant Synthesis of Netrin-1 in Satellite Cell-Derived Myoblasts Isolated from EDL Rather Than Soleus Muscle Regulates Fast-Type Myotube Formation.

Resident myogenic stem cells (satellite cells) are attracting attention for their novel roles in myofiber type regulation. In the myogenic differentiation phase, satellite cells from soleus muscle (slow fiber-abundant) synthesize and secrete higher levels of semaphorin 3A (Sema3A, a multifunctional modulator) than those derived from extensor digitorum longus (EDL; fast fiber-abundant), suggesting the role of Sema3A in forming slow-twitch myofibers. However, the regulatory mechanisms underlying fast-twitch myotube commitment remain unclear.

Epigenetic effects induced by the ectopic expression of Pax7 in 3T3-L1.

Although skeletal muscle cells and adipocytes are derived from the same mesoderm, they do not transdifferentiate in vivo and are strictly distinct at the level of gene expression. To elucidate some of the regulatory mechanisms underlying this strict distinction, Pax7, a myogenic factor, was ectopically expressed in 3T3-L1 adipose progenitor cells to perturb their adipocyte differentiation potential. Transcriptome analysis showed that ectopic expression of Pax7 repressed the expression of some adipocyte genes and induced expression of some skeletal muscle cell genes.

Premature satellite cell activation before injury accelerates myogenesis and disrupts neuromuscular junction maturation in regenerating muscle.

Satellite cell (SC) activation, mediated by nitric oxide (NO), is essential to myogenic repair, whereas myotube function requires innervation. Semaphorin (Sema) 3A, a neuro-chemorepellent, is thought to regulate axon guidance to neuromuscular junctions (NMJs) during myotube differentiation. We tested whether "premature" SC activation (SC activation before injury) by a NO donor (isosorbide dinitrate) would disrupt early myogenesis and/or NMJs.

Beef extract supplementation promotes myoblast proliferation and myotube growth in C2C12 cells.

Purpose: We previously determined that the intake of beef extract for 4 weeks increases skeletal muscle mass in rats. Thus, this study aimed to clarify whether beef extract has a hypertrophic effect on muscle cells and to determine the signaling pathway underlying beef extract-induced myotube hypertrophy.

Methods: We assessed the effects of beef extract supplement on mouse C2C12 skeletal muscle cell proliferation and differentiation and myotube growth.

Effect of Gender, Rearing, and Cooking on the Metabolomic Profile of Porcine Muscles.

To clarify the relationship between the fiber type composition and meat quality, we performed metabolomic analysis using porcine longissimus dorsi (LD) muscles. In the LD of pigs raised outdoors, the expression of myosin heavy chain (MyHC)1 (slow-twitch fiber marker protein) was significantly increased compared with that of MyHC1 in pigs raised in an indoor pen, suggesting that rearing outdoors could be considered as an exercise treatment. These LD samples were subjected to metabolomic analysis for examining the profile of most primary and secondary metabolites.

Increase in muscle endurance in mice by dietary Yamabushitake mushroom (Hericium erinaceus) possibly via activation of PPARδ.

Skeletal muscle fiber is largely classified into two types: type 1 (slow-twitch) and type 2 (fast-twitch) fibers. Meat quality and composition of fiber types are thought to be closely related. Previous research showed that overexpression of constitutively active peroxisome proliferator-activated receptor (PPAR)δ, a nuclear receptor present in skeletal muscle, increased type 1 fibers in mice.

Correlation between skeletal muscle fiber type and free amino acid levels in Japanese Black steers.

Free amino acids are important components of tastants and flavor precursors in meat. To clarify the correlation between muscle fiber type and free amino acids, we determined the concentrations of various free amino acids and dipeptides in samples of different muscle tissues (n = 21), collected from 26-month-old Japanese Black steers (n = 3) at 2 days postmortem. The proportions of the myosin heavy chain (MyHC), slow (MyHC1) and fast (MyHC2) isoforms were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).

Isolation and Purification of Satellite Cells from Young Rats by Percoll Density Gradient Centrifugation.

Satellite cells (SCs) are myogenic stem cells that play an important role in skeletal muscle regeneration and hypertrophy. Primary cultures of SCs are useful to analyze cell functions; however, it is difficult to obtain highly pure SCs from young rats with the conventional procedures. The purpose of this study is to establish a purification method for SC isolation from young rats and quantitatively evaluate the purification procedure employing Percoll, a common research tool to purify cells.

Dietary apple polyphenols increase skeletal muscle capillaries in Wistar rats.

Dietary apple polyphenols (AP) have been shown to exhibit beneficial effects on muscle endurance. Fast-to-slow change in the composition of myosin heavy chains was known as one of the molecular mechanisms. Here, we examined the effects of dietary AP on the capillaries and mitochondria in the rat skeletal muscle to elucidate the mechanisms underlying muscular endurance enhancement.

Paired box 7 inhibits differentiation in 3T3-L1 preadipocytes.

Myogenesis is precisely proceeded by myogenic regulatory factors. Myogenic stem cells are activated, proliferated and fused into a multinuclear myofiber. Pax7, paired box 7, one of the earliest markers during myogenesis.

Fluorescence microscopy data on expression of Paired Box Transcription Factor 7 in skeletal muscle of APOBEC2 knockout mice.

The data presented in this article are related to the research articles entitled "APOBEC2 negatively regulates myoblast differentiation in muscle regeneration" and "Data supporting possible implication of APOBEC2 in self-renewal functions of myogenic stem satellite cells: toward understanding the negative regulation of myoblast differentiation" (Ohtsubo et al., 2017a, 2017b) [1,2]. This article provides phenotypical data to show that Paired Box Transcription Factor 7 (Pax7)-positive cell number (per myofiber) is significantly lower in APOBEC2 (a member of apoB mRNA editing enzyme, catalytic polypeptide-like family)-knockout muscle than the control wild-type tissue at the same age of 8-wk-old in mice.

Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle.

Apobec2 is a member of the activation-induced deaminase/apolipoprotein B mRNA editing enzyme catalytic polypeptide cytidine deaminase family expressed in differentiated skeletal and cardiac muscle. We previously reported that Apobec2 deficiency in mice leads to a shift in muscle fiber type, myopathy, and diminished muscle mass. However, the mechanisms of myopathy caused by Apobec2 deficiency and its physiologic functions are unclear.

Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells.

Recently, we found that resident myogenic stem satellite cells upregulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early-differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) → myogenin-myocyte enhancer factor 2D → slow myosin heavy chain. This novel axis was found by small interfering RNA-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression.

Data supporting possible implication of APOBEC2 in self-renewal functions of myogenic stem satellite cells: Toward understanding the negative regulation of myoblast differentiation.

This paper provides phenotypical data to show that APOBEC2, a member of apoB mRNA editing enzyme, catalytic polypeptide-like family, may implicate in self-renewal functions of myogenic stem satellite cells, namely in the re-establishment of quiescent status after activation and proliferation of myoblasts in single-myofiber culture.

Mouse soleus (slow) muscle shows greater intramyocellular lipid droplet accumulation than EDL (fast) muscle: fiber type-specific analysis.

Skeletal muscle is the main tissue of lipid metabolism and accordingly is critical for homeostasis and energy production; however, the determinants of lipid accumulation in skeletal muscle are unknown. Here, we examined whether the soleus muscle (predominantly slow-twitch fibers) has a higher lipid accumulation capacity than that of the extensor digitorum longus (EDL, predominantly fast-twitch fibers) muscle in mice. Soleus and EDL muscles were harvested from male C57BL/6J mice.

APOBEC2 negatively regulates myoblast differentiation in muscle regeneration.

Recently we found that the deficiency of APOBEC2, a member of apoB mRNA editing enzyme, catalytic polypeptide-like family, leads to a diminished muscle mass and increased myofiber with centrally-located nuclei known as dystrophic phenotypes. APOBEC2 expression is predominant in skeletal and cardiac muscles and elevated exclusively at the early-differentiation phase of wild-type (WT) myoblast cultures; however the physiological significance is still un-known. Here we show that APOBEC2 is a key negative regulator of myoblast differentiation in muscle regeneration.