Evidence for acute contraction-induced myokine secretion by C2C12 myotubes

Furuichi, Yukio; Manabe, Yasuko; Takagi, Mayumi; Aoki, Miho; Fujii, Nobuharu

doi:10.1371/journal.pone.0206146

Cited by 40 publications

(44 citation statements)

References 39 publications

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“…Gene expression results show that EGR1, IL6, FOS, HSPB1, and mdm2 increased after 20-Hz EPS. These genes were known to increase after exercise or EPS ( Furuichi et al., 2018 ; Irrcher and Hood, 2004 ; Neubauer et al., 2014 ; Roudier et al., 2012 ). Gene expression of dgkq, Pik3r1, PIK3C2B, and Thbs1 decreased after 20-Hz EPS.…”

Section: Discussionmentioning

confidence: 99%

Trans-omic Analysis Reveals ROS-Dependent Pentose Phosphate Pathway Activation after High-Frequency Electrical Stimulation in C2C12 Myotubes

et al. 2020

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Summary Skeletal muscle adaptation is mediated by cooperative regulation of metabolism, signal transduction, and gene expression. However, the global regulatory mechanism remains unclear. To address this issue, we performed electrical pulse stimulation (EPS) in differentiated C2C12 myotubes at low and high frequency, carried out metabolome and transcriptome analyses, and investigated phosphorylation status of signaling molecules. EPS triggered extensive and specific changes in metabolites, signaling phosphorylation, and gene expression during and after EPS in a frequency-dependent manner. We constructed trans-omic network by integrating these data and found selective activation of the pentose phosphate pathway including metabolites, upstream signaling molecules, and gene expression of metabolic enzymes after high-frequency EPS. We experimentally validated that activation of these molecules after high-frequency EPS was dependent on reactive oxygen species (ROS). Thus, the trans-omic analysis revealed ROS-dependent activation in signal transduction, metabolome, and transcriptome after high-frequency EPS in C2C12 myotubes, shedding light on possible mechanisms of muscle adaptation.

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Section: Discussionmentioning

confidence: 99%

Trans-omic Analysis Reveals ROS-Dependent Pentose Phosphate Pathway Activation after High-Frequency Electrical Stimulation in C2C12 Myotubes

et al. 2020

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“…Furthermore, several studies reported that the change of IL-6 in muscle and in circulation is not consistent [5,6,10,27]. Furuichi et al also have reported that IL-6 release from C2C12 cells which is the murine-derived skeletal muscle cell line is induced by electrical stimulation independently of intracellular IL-6 protein levels of C2C12 cells lysate [9]. These studies suggest that muscle IL-6 release is induced independently of the transcription.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that IL-6 is produced by myocytes during endurance exercise [6,8]. Electrical stimulation of C2C12 cells (a murine-derived skeletal muscle cell line) also stimulates IL-6 production in vitro [9]. However, IL-6 exists in interstitial spaces, as detected by immunohistochemistry [6], suggesting that non-myocyte cells may also produce IL-6.…”

Section: Introductionmentioning

confidence: 99%

Glucose Ingestion Inhibits Endurance Exercise-Induced IL-6 Producing Macrophage Infiltration in Mice Muscle

Tominaga

Saitou

2019

Nutrients

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Background: Carbohydrate (CHO) supplementation during exercise attenuates exercise-induced increases in plasma Interleukin (IL)-6 concentration. However, the effects of CHO supplementation on muscle IL-6 production during endurance exercise is controversial. The purpose of this study was to investigate the effects of CHO supplementation on muscle IL-6 production during endurance exercise with a special focus on the IL-6 producing cells. Methods: C57BL/6J mice were divided into three groups—sedentary with water ingestion group as the control (Con; n = 10), exercise with water ingestion group (Ex; n = 10), and exercise with 6% glucose ingestion group (Ex + glucose; n = 10). The Ex and Ex + glucose groups completed 3 h of treadmill running (24 m/min, 7% incline) and were sacrificed immediately after exercise. Results: The exercise-induced increases of plasma IL-6 concentration and gastrocnemius IL-6 gene expression were attenuated by glucose ingestion. However, the increases of soleus IL-6 gene expression and gastrocnemius and soleus IL-6 protein expression were not attenuated by glucose ingestion. Furthermore, we observed that macrophages that infiltrated muscle produce IL-6 and glucose ingestion attenuated the infiltration of IL-6-producing macrophages. Conclusion: This study revealed that infiltrating macrophages may be one type of IL-6-producing cells during endurance exercise, and the infiltration of these cells in muscle was attenuated by glucose ingestion. However, the effects of glucose ingestion on muscle IL-6 production were limited.

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“…Lactic acid concentration in the medium increased due to contraction (Fig 1C), while glucose concentration decreased (Fig 1D). We have previously shown that acute contractions by 1 h EPS induced IL-6 and IL-15 secretions from C2C12 myotubes in Krebs Ringer bicarbonate (KRB) buffer [18]. However, the amount of IL-6 and IL-15 in the medium was unchanged under the present EPS protocol (Fig 1E and 1F).…”

Section: Plos Onementioning

confidence: 56%

“…The secretion of IL-6 and IL-15 was unchanged under the present EPS protocols ( Fig 1E and 1F ). The difference may depend on the medium, as KRB buffer, rather than DMEM, is suitable for detecting IL-6 secretion [ 18 ]. Regardless, it is unlikely that these proteins affected adipogenesis or lipolysis in the present experiment system, even though it has been reported that IL-6 and IL-15 reduce adiposity [ 6 – 9 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of treatment with conditioned media derived from C2C12 myotube on adipogenesis and lipolysis in 3T3-L1 adipocytes

et al. 2020

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Regular exercise is an effective strategy that is used to prevent and treat obesity as well as type 2 diabetes. Exercise-induced myokine secretion is considered a mechanism that coordinates communication between muscles and other organs. In order to examine the possibility of novel communications from muscle to adipose tissue mediated by myokines, we treated 3T3-L1 adipocytes with C2C12 myotube electrical pulse stimulation-conditioned media (EPS-CM), using a C2C12 myotube contraction system stimulated by an electrical pulse. Continuous treatment with myotube EPS-CM promoted adipogenesis of 3T3-L1 preadipocytes via the upregulation of the peroxisome proliferator-activated receptor-gamma (PPARγ) 2 and PPARγ-regulated gene expression. Furthermore, our results revealed that myotube EPS-CM induces lipolysis and secretion of adiponectin in mature adipocytes. EPS-CM obtained from a C2C12 myoblast culture did not induce such changes in these genes, suggesting that contraction-induced myokine(s) secretion occurs particularly in differentiated myotubes. Thus, contraction-induced secretion of myokine(s) promotes adipogenesis and lipid metabolism in 3T3-L1 adipocytes. These findings suggest the possibility that skeletal muscle communicates to adipose tissues during exercise, probably by the intermediary of unidentified myokines.

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Evidence for acute contraction-induced myokine secretion by C2C12 myotubes

Cited by 40 publications

References 39 publications

Trans-omic Analysis Reveals ROS-Dependent Pentose Phosphate Pathway Activation after High-Frequency Electrical Stimulation in C2C12 Myotubes

Trans-omic Analysis Reveals ROS-Dependent Pentose Phosphate Pathway Activation after High-Frequency Electrical Stimulation in C2C12 Myotubes

Glucose Ingestion Inhibits Endurance Exercise-Induced IL-6 Producing Macrophage Infiltration in Mice Muscle

Effect of treatment with conditioned media derived from C2C12 myotube on adipogenesis and lipolysis in 3T3-L1 adipocytes

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