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

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.

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Skeletal muscle atrophy contributes to exercise intolerance in heart failure

Journal of the American College of Cardiology ◽

10.1016/0735-1097(91)91318-9 ◽

1991 ◽

Vol 17 (2) ◽

pp. A88

Author(s):

Donna M. Mancini ◽

Deborah Nazzaro ◽

Lynne Georgopoulos ◽

Nancy Wagner ◽

James L. Mullen ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Muscle Atrophy ◽

Exercise Intolerance ◽

Skeletal Muscle Atrophy

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

Nutrients ◽

10.3390/nu12082274 ◽

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.

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Triptolide prevents lipopolysaccharide‐induced skeletal muscle atrophy via inhibiting NF‐κB/TNF‐α and regulating protein synthesis/degradation pathway

British Journal of Pharmacology ◽

10.1111/bph.15472 ◽

2021 ◽

Author(s):

Wei‐Yu Fang ◽

Yu‐Ting Tseng ◽

Tzu‐Ying Lee ◽

Yin‐Chih Fu ◽

Wan‐Hsuan Chang ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Atrophy ◽

Degradation Pathway ◽

Skeletal Muscle Atrophy ◽

Tnf Α

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

Nutrients ◽

10.3390/nu14010104 ◽

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.

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Long Term Adrenal Insufficiency Induces Skeletal Muscle Atrophy and Increases the Serum Levels of Active Form Myostatin in Rat Serum

ZOOLOGICAL SCIENCE ◽

10.2108/zsj.22.229 ◽

2005 ◽

Vol 22 (2) ◽

pp. 229-236 ◽

Cited By ~ 10

Author(s):

Tohru Hosoyama ◽

Chikashi Tachi ◽

Keitaro Yamanouchi ◽

Masugi Nishihara

Keyword(s):

Skeletal Muscle ◽

Adrenal Insufficiency ◽

Muscle Atrophy ◽

Active Form ◽

Serum Levels ◽

Skeletal Muscle Atrophy ◽

Rat Serum

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

10.21203/rs.3.rs-1213317/v1 ◽

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.

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Skeletal Muscle Atrophy and Peak Oxygen Consumption in Heart Failure

The American Journal of Cardiology ◽

10.1016/s0002-9149(97)00098-2 ◽

1997 ◽

Vol 79 (9) ◽

pp. 1267-1269 ◽

Cited By ~ 48

Author(s):

Michael J. Toth ◽

Stephen S. Gottlieb ◽

Michael L. Fisher ◽

Eric T. Poehlman

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Oxygen Consumption ◽

Muscle Atrophy ◽

Peak Oxygen Consumption ◽

Skeletal Muscle Atrophy

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Exercise training decreases NADPH oxidase activity and restores skeletal muscle mass in heart failure rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00182.2016 ◽

2017 ◽

Vol 122 (4) ◽

pp. 817-827 ◽

Cited By ~ 18

Author(s):

Telma F. Cunha ◽

Luiz R. G. Bechara ◽

Aline V. N. Bacurau ◽

Paulo R. Jannig ◽

Vanessa A. Voltarelli ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Exercise Training ◽

Nadph Oxidase ◽

Protein Degradation ◽

Muscle Atrophy ◽

Oxidase Activity ◽

Proteasome Activity ◽

Skeletal Muscle Atrophy ◽

Nadph Oxidase Activity

We have recently demonstrated that NADPH oxidase hyperactivity, NF-κB activation, and increased p38 phosphorylation lead to atrophy of glycolytic muscle in heart failure (HF). Aerobic exercise training (AET) is an efficient strategy to counteract skeletal muscle atrophy in this syndrome. Therefore, we tested whether AET would regulate muscle redox balance and protein degradation by decreasing NADPH oxidase hyperactivity and reestablishing NF-κB signaling, p38 phosphorylation, and proteasome activity in plantaris muscle of myocardial infarcted-induced HF (MI) rats. Thirty-two male Wistar rats underwent MI or fictitious surgery (SHAM) and were randomly assigned into untrained (UNT) and trained (T; 8 wk of AET on treadmill) groups. AET prevented HF signals and skeletal muscle atrophy in MI-T, which showed an improved exercise tolerance, attenuated cardiac dysfunction and increased plantaris fiber cross-sectional area. To verify the role of inflammation and redox imbalance in triggering protein degradation, circulating TNF-α levels, NADPH oxidase profile, NF-κB signaling, p38 protein levels, and proteasome activity were assessed. MI-T showed a reduced TNF-α levels, NADPH oxidase activity, and Nox2 mRNA expression toward SHAM-UNT levels. The rescue of NADPH oxidase activity induced by AET in MI rats was paralleled by reducing nuclear binding activity of the NF-κB, p38 phosphorylation, atrogin-1, mRNA levels, and 26S chymotrypsin-like proteasome activity. Taken together our data provide evidence for AET improving plantaris redox homeostasis in HF associated with a decreased NADPH oxidase, redox-sensitive proteins activation, and proteasome hyperactivity further preventing atrophy. These data reinforce the role of AET as an efficient therapy for muscle wasting in HF. NEW & NOTEWORTHY This study demonstrates, for the first time, the contribution of aerobic exercise training (AET) in decreasing muscle NADPH oxidase activity associated with reduced reactive oxygen species production and systemic inflammation, which diminish NF-κB overactivation, p38 phosphorylation, and ubiquitin proteasome system hyperactivity. These molecular changes counteract plantaris atrophy in trained myocardial infarction-induced heart failure rats. Our data provide new evidence into how AET may regulate protein degradation and thus prevent skeletal muscle atrophy.

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