scholarly journals Skeletal Muscle Atrophy is Exacerbated By Steatotic and Fibrotic Liver-Derived TNF-Alpha in Senescence-Accelerated Mice

2022 ◽  
Author(s):  
Yohei Shirakami ◽  
Junichi Kato ◽  
Toshihide Maeda ◽  
Takayasu Ideta ◽  
Hiroyasu Sakai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Liver Diseases ◽  
Control Diet ◽  
Diet Group ◽  
Skeletal Muscle Atrophy ◽  
Fibrotic Liver ◽  
Nash Group ◽  
Tnf Α ◽  
Senescence Accelerated Mice

Abstract Although liver diseases, including non-alcoholic steatohepatitis (NASH), are associated with skeletal muscle atrophy, the mechanism behind their association has not been fully elucidated. In this study, the effects of aging and NASH on the skeletal muscle and the interaction between the liver and muscle were investigated using a diet-induced NASH model in senescence-accelerated mice (SAM). A total of four groups of SAM and its control mice were fed either an NASH-inducing or control diet. In the SAM/NASH group, the histopathology of NASH and markers of oxidative stress were significant. Skeletal muscles were also markedly atrophied. The expression of the ubiquitin ligase Murf1 in the muscle was significantly increased with muscle atrophy, while that of Tnfa was not significantly different. In contrast, the hepatic Tnfa expression and serum TNF-α levels were significantly increased in the SAM/NASH group. These results suggest that liver-derived TNF-α might promote muscle atrophy associated with steatohepatitis and aging through Murf-1. The metabolomic analysis of skeletal muscle indicated higher spermidine and lower tryptophan levels in the NASH-diet group. The findings of this study revealed an aspect of liver-muscle interaction, which might be important in developing treatments for sarcopenia associated with liver diseases.

scholarly journals Preclinical Evaluation of a Food-Derived Functional Ingredient to Address Skeletal Muscle Atrophy

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2274
Author(s):  
Roi Cal ◽  
Heidi Davis ◽  
Alish Kerr ◽  
Audrey Wall ◽  
Brendan Molloy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Murine Model ◽  
The Body ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Disuse Atrophy ◽  
Tnf Α

Skeletal muscle is the metabolic powerhouse of the body, however, dysregulation of the mechanisms involved in skeletal muscle mass maintenance can have devastating effects leading to many metabolic and physiological diseases. The lack of effective solutions makes finding a validated nutritional intervention an urgent unmet medical need. In vitro testing in murine skeletal muscle cells and human macrophages was carried out to determine the effect of a hydrolysate derived from vicia faba (PeptiStrong: NPN_1) against phosphorylated S6, atrophy gene expression, and tumour necrosis factor alpha (TNF-α) secretion, respectively. Finally, the efficacy of NPN_1 on attenuating muscle waste in vivo was assessed in an atrophy murine model. Treatment of NPN_1 significantly increased the phosphorylation of S6, downregulated muscle atrophy related genes, and reduced lipopolysaccharide-induced TNF-α release in vitro. In a disuse atrophy murine model, following 18 days of NPN_1 treatment, mice exhibited a significant attenuation of muscle loss in the soleus muscle and increased the integrated expression of Type I and Type IIa fibres. At the RNA level, a significant upregulation of protein synthesis-related genes was observed in the soleus muscle following NPN_1 treatment. In vitro and preclinical results suggest that NPN_1 is an effective bioactive ingredient with great potential to prolong muscle health.

scholarly journals Magnesium Lithospermate B Attenuates High-Fat Diet-Induced Muscle Atrophy in C57BL/6J Mice

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 104
Author(s):  
Tsun-Li Cheng ◽  
Zi-Yun Lin ◽  
Keng-Ying Liao ◽  
Wei-Chi Huang ◽  
Cian-Fen Jhuo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
High Fat Diet ◽  
Skeletal Muscle Atrophy ◽  
Metabolic Abnormalities ◽  
High Fat ◽  
E3 Ligases ◽  
Beneficial Effects ◽  
Magnesium Lithospermate B ◽  
Tnf Α

Magnesium lithospermate B (MLB) is a primary hydrophilic component of Danshen, the dried root of Salvia miltiorrhiza used in traditional medicine, and its beneficial effects on obesity-associated metabolic abnormalities were reported in our previous study. The present study investigated the anti-muscle atrophy potential of MLB in mice with high-fat diet (HFD)-induced obesity. In addition to metabolic abnormalities, the HFD mice had a net loss of skeletal muscle weight and muscle fibers and high levels of muscle-specific ubiquitin E3 ligases, namely the muscle atrophy F-box (MAFbx) and muscle RING finger protein 1 (MuRF-1). MLB supplementation alleviated those health concerns. Parallel changes were revealed in high circulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), skeletal TNF receptor I (TNFRI), nuclear factor-kappa light chain enhancer of activated B cells (NF-κB), p65 phosphorylation, and Forkhead box protein O1 (FoxO1) as well as low skeletal phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) phosphorylation. The study revealed that MLB prevented obesity-associated skeletal muscle atrophy, likely through the inhibition of MAFbx/MuRF-1-mediated muscular degradation. The activation of the PI3K-Akt-FoxO1 pathway and inhibition of the TNF-α/TNFRI/NF-κB pathway were assumed to be beneficial effects of MLB.

scholarly journals Liver fibrosis-induced muscle atrophy is mediated by elevated levels of circulating TNFα

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tamaki Kurosawa ◽  
Momo Goto ◽  
Noriyuki Kaji ◽  
Satoshi Aikiyo ◽  
Taiki Mihara ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Liver Cirrhosis ◽  
Liver Fibrosis ◽  
Muscle Atrophy ◽  
Diploid Cell ◽  
Serum Levels ◽  
Skeletal Muscle Atrophy ◽  
Mouse Serum ◽  
Fibrotic Liver ◽  
Duct Ligation

AbstractLiver cirrhosis is a critical health problem associated with several complications, including skeletal muscle atrophy, which adversely affects the clinical outcome of patients independent of their liver functions. However, the precise mechanism underlying liver cirrhosis-induced muscle atrophy has not been elucidated. Here we show that serum factor induced by liver fibrosis leads to skeletal muscle atrophy. Using bile duct ligation (BDL) model of liver injury, we induced liver fibrosis in mice and observed subsequent muscle atrophy and weakness. We developed culture system of human primary myotubes that enables an evaluation of the effects of soluble factors on muscle atrophy and found that serum from BDL mice contains atrophy-inducing factors. This atrophy-inducing effect of BDL mouse serum was mitigated upon inhibition of TNFα signalling but not inhibition of myostatin/activin signalling. The BDL mice exhibited significantly up-regulated serum levels of TNFα when compared with the control mice. Furthermore, the mRNA expression levels of Tnf were markedly up-regulated in the fibrotic liver but not in the skeletal muscles of BDL mice. The gene expression analysis of isolated nuclei revealed that Tnf is exclusively expressed in the non-fibrogenic diploid cell population of the fibrotic liver. These findings reveal the mechanism through which circulating TNFα produced in the damaged liver mediates skeletal muscle atrophy. Additionally, this study demonstrated the importance of inter-organ communication that underlies the pathogenesis of liver cirrhosis.

scholarly journals MON-724 Crude Protein Extract of Pyropia Yezoensis Protects Against Tumor Necrosis Factor-á-Induced Apoptosis and Atrophy in C2C12 Myotubes

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Min-Kyeong Lee ◽  
Taek-Jeong Nam ◽  
Youn Hee Choi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Crude Protein ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Necrosis Factor

Abstract Proinflammatory cytokines such as tumor necrosis factor (TNF)-α play an important role in the development of skeletal muscle atrophy, and TNF-α-induced apoptosis may mediate skeletal muscle atrophy. Therefore, we evaluated the effect of Pyropia yezoensis crude protein (PYCP) on TNF-α-induced apoptosis and identified the involved signaling pathways. For this purpose, C2C12 myotubes were treated with 20 ng/mL TNF-α in the presence or absence of 25-100 μg/mL PYCP for 48 h. Treatment with TNF-α markedly increased the protein level of TNF-receptor 1 (TNF-R1). In contrast, treatment with PYCP downregulated the TNF-α-induced increase in the TNF-R1 protein level. Also, the expression of Bax, Bcl-2, cytochrome C, and apoptosis-inducing factor, markers of apoptosis in myofibers, was increased by TNF-α, but this effect was inhibited by PYCP in a concentration-dependent manner. In addition, exposure of C2C12 myotubes to TNF-α for 48 h enhanced the activity of caspase-3, which was significantly inhibited by PYCP. Furthermore, poly[ADP-ribose] polymerase cleavage and histone-associated DNA fragmentation were markedly increased by TNF-α and attenuated by PYCP in a concentration-dependent manner. In conclusion, the ability of PYCP to inhibit the apoptosis induced by TNF-α suggests that it has therapeutic potential for skeletal muscle atrophy.

Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure

2004 ◽  
Vol 286 (1) ◽  
pp. C138-C144 ◽  
Author(s):  
Luciano Dalla Libera ◽  
Barbara Ravara ◽  
Maurizio Volterrani ◽  
Valerio Gobbo ◽  
Mila Della Barbera ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Muscle Atrophy ◽  
Serum Levels ◽  
Skeletal Muscle Atrophy ◽  
Gh Treatment ◽  
Tnf Α ◽  
Myocyte Apoptosis ◽  
Contraction And Relaxation

Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-α (TNF-α) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear. We tested the hypothesis that GH can prevent skeletal muscle apoptosis in rats with CHF. CHF was induced by injecting monocrotaline. After 2 wk, 2 groups of rats were treated with GH (0.2 mg·kg–1·day–1 and 1.0 mg·kg–1·day–1) subcutaneously. A third group of controls had saline. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, myosin heavy chain (MHC) composition, and a study on myocyte apoptosis and serum levels of TNF-α and SPH were carried out. The number of apoptotic nuclei, muscle atrophy, and serum levels of TNF-α and SPH were decreased with GH at high but not at low doses compared with CHF rats. Bcl-2 was increased, whereas activated caspases and bax were decreased. The MHC pattern in GH-treated animals was similar to that of controls. Monocrotaline slowed down both contraction and relaxation but did not affect specific tetanic force, whereas absolute force was decreased. GH treatment restored contraction and relaxation to control values and brought muscle mass and absolute twitch and tetanic tension to normal levels. These findings may provide an insight into the therapeutic strategy of GH given to patients with CHF to improve exercise capacity.

scholarly journals Salidroside mitigates skeletal muscle atrophy in rats with cigarette smoke-induced COPD by up-regulating myogenin and down-regulating myostatin expression

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Dan Zhang ◽  
Lihua Cao ◽  
Zhenshan Wang ◽  
Haoshen Feng ◽  
Xu Cai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lung Function ◽  
Cigarette Smoking ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
High Dose ◽  
Air Exposure ◽  
Tnf Α ◽  
Healthy Control

Abstract Objectives: The present study aimed at investigating the therapeutic effect of Salidroside on skeletal muscle atrophy in a rat model of cigarette smoking-induced chronic obstructive pulmonary disease (COPD) and its potential mechanisms. Methods: Male Wistar rats were randomized, and treated intraperitoneally (IP) with vehicle (injectable water) or a low, medium or high dose of Salidroside, followed by exposure to cigarette smoking daily for 16 weeks. A healthy control received vehicle injection and air exposure. Their lung function, body weights and gastrocnemius (GN) weights, grip strength and cross-section area (CSA) of individual muscular fibers in the GN were measured. The levels of TNF-α, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) in serum and GN tissues as well as myostatin and myogenin expression in GN tissues were measured. Results: In comparison with that in the healthy control, long-term cigarette smoking induced emphysema, significantly impaired lung function, reduced body and GN weights and CSA values in rats, accompanied by significantly increased levels of TNF-α, IL-6 and MDA, but decreased levels of SOD and GSH in serum and GN tissues. Furthermore, cigarette smoking significantly up-regulated myostatin expression, but down-regulated myogenin expression in GN tissues. Salidroside treatment decreased emphysema, significantly ameliorated lung function, increased antioxidant, but reduced MDA, IL-6 and TNF-α levels in serum and GN tissues of rats, accompanied by decreased myostain, but increased myogenin expression in GN tissues. Conclusion: Salidroside mitigates the long-term cigarette smoking-induced emphysema and skeletal muscle atrophy in rats by inhibiting oxidative stress and inflammatory responses and regulating muscle-specific transcription factor expression.

scholarly journals GH-Releasing Hormone Promotes Survival and Prevents TNF-α-Induced Apoptosis and Atrophy in C2C12 Myotubes

Endocrinology ◽  
2015 ◽  
Vol 156 (9) ◽  
pp. 3239-3252 ◽  
Author(s):  
Davide Gallo ◽  
Iacopo Gesmundo ◽  
Letizia Trovato ◽  
Giulia Pera ◽  
Eleonora Gargantini ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Glycogen Synthase ◽  
Muscle Protein ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Tnf Α ◽  
Induced Apoptosis

Skeletal muscle atrophy is a consequence of different chronic diseases, including cancer, heart failure, and diabetes, and also occurs in aging and genetic myopathies. It results from an imbalance between anabolic and catabolic processes, and inflammatory cytokines, such as TNF-α, have been found elevated in muscle atrophy and implicated in its pathogenesis. GHRH, in addition to stimulating GH secretion from the pituitary, exerts survival and antiapoptotic effects in different cell types. Moreover, we and others have recently shown that GHRH displays antiapoptotic effects in isolated cardiac myocytes and protects the isolated heart from ischemia/reperfusion injury and myocardial infarction in vivo. On these bases, we investigated the effects of GHRH on survival and apoptosis of TNF-α-treated C2C12 myotubes along with the underlying mechanisms. GHRH increased myotube survival and prevented TNF-α-induced apoptosis through GHRH receptor-mediated mechanisms. These effects involved activation of phosphoinositide 3-kinase/Akt pathway and inactivation of glycogen synthase kinase-3β, whereas mammalian target of rapamycin was unaffected. GHRH also increased the expression of myosin heavy chain and the myogenic transcription factor myogenin, which were both reduced by the cytokine. Furthermore, GHRH inhibited TNF-α-induced expression of nuclear factor-κB, calpain, and muscle ring finger1, which are all involved in muscle protein degradation. In summary, these results indicate that GHRH exerts survival and antiapoptotic effects in skeletal muscle cells through the activation of anabolic pathways and the inhibition of proteolytic routes. Overall, our findings suggest a novel therapeutic role for GHRH in the treatment of muscle atrophy-associated diseases.

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