scholarly journals Sphingosine-1-phosphate analog FTY720 reverses obesity but not age-induced anabolic resistance to muscle contraction

2019 ◽  
Vol 317 (3) ◽  
pp. C502-C512
Author(s):  
Donato A. Rivas ◽  
Nicholas P. Rice ◽  
Yassine Ezzyat ◽  
Devin J. McDonald ◽  
Brittany E. Cooper ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Muscle Contraction ◽  
Chronic Inflammation ◽  
Muscle Atrophy ◽  
Muscle Cells ◽  
Skeletal Muscle Atrophy ◽  
Anabolic Resistance ◽  
Sphingosine 1 Phosphate

Sarcopenia, the age-associated loss of skeletal muscle mass and function, is coupled with declines in physical functioning leading to subsequent higher rates of disability, frailty, morbidity, and mortality. Aging and obesity independently contribute to muscle atrophy that is assumed to be a result of the activation of mutual physiological pathways. Understanding mechanisms contributing to the induction of skeletal muscle atrophy with aging and obesity is important for determining targets that may have pivotal roles in muscle loss in these conditions. We find that aging and obesity equally induce an anabolic resistance to acute skeletal muscle contraction as observed with decreases in anabolic signaling activation after contraction. Furthermore, treatment with the sphingosine-1-phosphate analog FTY720 for 4 wk increased lean mass and strength, and the anabolic signaling response to contraction was improved in obese but not older animals. To determine the role of chronic inflammation and different fatty acids on anabolic resistance in skeletal muscle cells, we overexpressed IKKβ with and without exposure to saturated fatty acid (SFA; palmitic acid), polyunsaturated fatty acid (eicosapentaenoic acid), and monounsaturated fatty acid (oleic acid). We found that IKKβ overexpression increased inflammation markers in muscle cells, and this chronic inflammation exacerbated anabolic resistance in response to SFA. Pretreatment with FTY720 reversed the inflammatory effects of palmitic acid in the muscle cells. Taken together, these data demonstrate chronic inflammation can induce anabolic resistance, SFA aggravates these effects, and FTY720 can reverse this by decreasing ceramide accumulation in skeletal muscle.

scholarly journals Tail suspension is useful as a sarcopenia model in rats

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Akira Nemoto ◽  
Toru Goyagi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Experimental Model ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Whole Body ◽  
Skeletal Muscle Atrophy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Simple Method

Abstract Background Sarcopenia promotes skeletal muscle atrophy and exhibits a high mortality rate. Its elucidation is of the highest clinical importance, but an animal experimental model remains controversial. In this study, we investigated a simple method for studying sarcopenia in rats. Results Muscle atrophy was investigated in 24-week-old, male, tail-suspended (TS), Sprague Dawley and spontaneously hypertensive rats (SHR). Age-matched SD rats were used as a control group. The skeletal muscle mass weight, muscle contraction, whole body tension (WBT), cross-sectional area (CSA), and Muscle RING finger-1 (MuRF-1) were assessed. Enzyme-linked immunosorbent assay was used to evaluate the MuRF-1 levels. Two muscles, the extensor digitorum longus and soleus muscles, were selected for representing fast and slow muscles, respectively. All data, except CSA, were analyzed by a one-way analysis of variance, whereas CSA was analyzed using the Kruskal-Wallis test. Muscle mass weight, muscle contraction, WBT, and CSA were significantly lower in the SHR (n = 7) and TS (n = 7) groups than in the control group, whereas MuRF-1 expression was dominant. Conclusions TS and SHR presented sarcopenic phenotypes in terms of muscle mass, muscle contraction and CSA. TS is a useful technique for providing muscle mass atrophy and weakness in an experimental model of sarcopenia in rats.

scholarly journals Involvement of released sphingosine 1-phosphate/sphingosine 1-phosphate receptor axis in skeletal muscle atrophy

2018 ◽  
Vol 1864 (12) ◽  
pp. 3598-3614 ◽  
Author(s):  
Federica Pierucci ◽  
Alessia Frati ◽  
Chiara Battistini ◽  
Francesca Matteini ◽  
Maria Chiara Iachini ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Sphingosine 1 Phosphate

Skeletal Muscle Atrophy Is Associated With Chronic Inflammation In The APCMin+/- Mouse

2005 ◽  
Vol 37 (Supplement) ◽  
pp. S32???S33
Author(s):  
Kristen A. Mchl ◽  
Joseph M. McClung ◽  
J. Mark Davis ◽  
Franklin G. Berger ◽  
James A. Carson
Keyword(s):  
Skeletal Muscle ◽  
Chronic Inflammation ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy

scholarly journals A time course for markers of protein synthesis and degradation with hindlimb unloading and the accompanying anabolic resistance to refeeding

2020 ◽  
Vol 129 (1) ◽  
pp. 36-46 ◽  
Author(s):  
Paul A. Roberson ◽  
Kevin L. Shimkus ◽  
Jaclyn E. Welles ◽  
Dandan Xu ◽  
Abigale L. Whitsell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Time Course ◽  
Hindlimb Unloading ◽  
Skeletal Muscle Atrophy ◽  
Anabolic Resistance ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Hindlimb unloading causes significant skeletal muscle atrophy by adversely affecting the balance between protein synthesis and breakdown. This study demonstrates a more complete time course for changes in biomarkers associated with protein synthesis and breakdown and investigates the associated anabolic resistance to an anabolic stimulus following hindlimb unloading. These data in concert with information from other studies provide a basis for designing future experiments to optimally interrogate a desired cellular biomarker or pathway.

scholarly journals Resistance exercise with anti-inflammatory foods attenuates skeletal muscle atrophy induced by chronic inflammation

2020 ◽  
Vol 128 (1) ◽  
pp. 197-211 ◽  
Author(s):  
Koichiro Sumi ◽  
Kinya Ashida ◽  
Koichi Nakazato
Keyword(s):  
Skeletal Muscle ◽  
Resistance Exercise ◽  
Chronic Inflammation ◽  
Muscle Atrophy ◽  
Inflammatory Responses ◽  
Muscle Protein ◽  
Dietary Supplementation ◽  
Skeletal Muscle Atrophy ◽  
Forkhead Box ◽  
Anti Inflammatory

Chronic inflammation (CI) can contribute to muscle atrophy and sarcopenia. Resistance exercise (RE) promotes increased and/or maintenance of skeletal muscle mass, but the effects of RE in the presence of CI are unclear. In this study, we developed a novel animal model of CI-induced muscle atrophy and examined the effect of acute or chronic RE by electrical stimulation. CI was induced in young female Lewis rats by injection with peptidoglycan-polysaccharide (PG-PS). Extracellular signal-regulated kinase (ERK), p70S6 kinase (p70S6K), 4E binding protein 1 (4E-BP1), Akt, and Forkhead box O1 (FOXO1) phosphorylation levels increased in gastrocnemius (Gas) muscle from normal rats subjected to acute RE. After acute RE in CI rats, increased levels of phosphorylated ERK, p70S6K, and 4E-BP1, but not Akt or FOXO1, were observed. Chronic RE significantly increased the Gas weight in the exercised limb relative to the nontrained opposing limb in CI rats. Dietary supplementation with anti-inflammatory agents, eicosapentaenoic/docosahexaenoic acid and α-lactalbumin attenuated CI-induced muscle atrophy in the untrained Gas and could promote RE-induced inhibition of atrophy in the trained Gas. In the trained leg, significant negative correlations ( r ≤ −0.80) were seen between Gas weights and CI indices, including proinflammatory cytokines and white blood cell count. These results indicated that the anabolic effects of RE are effective for preventing CI-induced muscle atrophy but are partially attenuated by inflammatory molecules. The findings also suggested that anti-inflammatory treatment together with RE is an effective intervention for muscle atrophy induced by CI. Taken together, we conclude that systemic inflammation levels are associated with skeletal muscle protein metabolism and plasticity. NEW & NOTEWORTHY This study developed a novel chronic inflammation (CI) model rat demonstrating that resistance exercise (RE) induced activation of protein synthesis signaling pathways and mitigated skeletal muscle atrophy. These anabolic effects were partially abrogated likely through attenuation of Akt/Forkhead box O1 axis activity. The degree of skeletal muscle atrophy was related to inflammatory responses. Dietary supplementation with anti-inflammatory agents could enhance the anabolic effect of RE. Our findings provide insight for development of countermeasures for CI-related muscle atrophy, especially secondary sarcopenia.

Dual-specificity phosphatase 29 is induced during neurogenic skeletal muscle atrophy and attenuates glucocorticoid receptor activity in muscle cell culture

2020 ◽  
Vol 319 (2) ◽  
pp. C441-C454
Author(s):  
Lisa M. Cooper ◽  
Rita C. West ◽  
Caleb S. Hayes ◽  
David S. Waddell
Keyword(s):  
Skeletal Muscle ◽  
Glucocorticoid Receptor ◽  
Reporter Gene ◽  
Muscle Cell ◽  
Muscle Atrophy ◽  
Muscle Cells ◽  
Proximal Promoter ◽  
Skeletal Muscle Atrophy ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity

Skeletal muscle atrophy is caused by a decrease in muscle size and strength and results from a range of physiological conditions, including denervation, immobilization, corticosteroid exposure and aging. Newly named dual-specificity phosphatase 29 ( Dusp29) has been identified as a novel neurogenic atrophy-induced gene in skeletal muscle. Quantitative PCR analysis revealed that Dusp29 expression is significantly higher in differentiated myotubes compared with proliferating myoblasts. To determine how Dusp29 is transcriptionally regulated in skeletal muscle, fragments of the promoter region of Dusp29 were cloned, fused to a reporter gene, and found to be highly inducible in response to ectopic expression of the myogenic regulatory factors (MRF), MyoD and myogenin. Furthermore, site-directed mutagenesis of conserved E-box elements within the proximal promoter of Dusp29 rendered a Dusp29 reporter gene unresponsive to MRF overexpression. Dusp29, an atypical Dusp also known as Dupd1/Dusp27, was found to attenuate the ERK1/2 branch of the MAP kinase signaling pathway in muscle cells and inhibit muscle cell differentiation when ectopically expressed in proliferating myoblasts. Interestingly, Dusp29 was also found to destabilize AMPK protein while simultaneously enriching the phosphorylated pool of AMPK in muscle cells. Additionally, Dusp29 overexpression resulted in a significant increase in the glucocorticoid receptor (GR) protein and elevation in GR phosphorylation. Finally, Dusp29 was found to significantly impair the ability of the glucocorticoid receptor to function as a transcriptional activator in muscle cells treated with dexamethasone. Identifying and characterizing the function of Dusp29 in muscle provides novel insights into the molecular and cellular mechanisms for skeletal muscle atrophy.

Skeletal Muscle Atrophy Is Associated With Chronic Inflammation In The APCMin+/- Mouse

2005 ◽  
Vol 37 (Supplement) ◽  
pp. S32-S33
Author(s):  
Kristen A. Mchl ◽  
Joseph M. McClung ◽  
J. Mark Davis ◽  
Franklin G. Berger ◽  
James A. Carson
Keyword(s):  
Skeletal Muscle ◽  
Chronic Inflammation ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy

P5.65 The effects of Omega-3 fatty acid on skeletal muscle atrophy induced by Dexamethasone

2011 ◽  
Vol 21 (9-10) ◽  
pp. 744
Author(s):  
A. Fappi ◽  
T.S. Godoy ◽  
D.P. Venâncio ◽  
G. Chadi ◽  
E. Zanoteli
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Omega 3 ◽  
Omega 3 Fatty Acid

scholarly journals Docosahexaenoic Acid Protects Muscle Cells from Palmitate-Induced Atrophy

ISRN Obesity ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Randall W. Bryner ◽  
Myra E. Woodworth-Hobbs ◽  
David L. Williamson ◽  
Stephen E. Alway
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Muscle Atrophy ◽  
Muscle Growth ◽  
Muscle Cells ◽  
Skeletal Muscle Atrophy ◽  
Omega 3 ◽  
Myotube Hypertrophy

Background. Accumulation of free fatty acids leads to lipid-toxicity-associated skeletal muscle atrophy. Palmitate treatment reduces myoblast and myotube growth and causes apoptosis in vitro. It is not known if omega-3 fatty acids will protect muscle cells against palmitate toxicity. Therefore, we examined the effects of docosahexaenoic acid (DHA) on skeletal muscle growth. Methods. Mouse myoblasts (C2C12) were differentiated to myotubes, and then treated with 0 or 0.5 mM palmitic acid or 0 or 0.1 mM DHA. Results. Intramyocellular lipid was increased in palmitate-treated cells but was prevented by DHA-palmitate cotreatment. Total AMPK increased in DHA+ palmitate-treated compared to palmitate only cells. RpS6 phosphorylation decreased after palmitate (−55%) and this was blunted by DHA+ palmitate (−35%) treatment. Palmitate treatment decreased PGC1 protein expression by 69%, but was increased 165% with DHA+ palmitate () versus palmitate alone. While palmitate induced 25% and 90% atrophy in myotubes (after 48 hours and 96 hours, resp.), DHA+ palmitate treatment caused myotube hypertrophy of ~50% and 100% after 48 and 96 hours, respectively. Conclusion. These data show that DHA is protective against palmitate-induced atrophy. Although DHA did not activate the AMPK pathway, DHA treatment restored growth-signaling (i.e., rpS6) and rescued palmitate-induced muscle atrophy.

scholarly journals Nutritional Strategies to Offset Disuse-Induced Skeletal Muscle Atrophy and Anabolic Resistance in Older Adults: From Whole-Foods to Isolated Ingredients

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1533 ◽  
Author(s):  
Ryan N. Marshall ◽  
Benoit Smeuninx ◽  
Paul T. Morgan ◽  
Leigh Breen
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Resistance Exercise ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Muscle Protein ◽  
Skeletal Muscle Atrophy ◽  
Older Individuals ◽  
Anabolic Resistance ◽  
Whole Foods

Preserving skeletal muscle mass and functional capacity is essential for healthy ageing. Transient periods of disuse and/or inactivity in combination with sub-optimal dietary intake have been shown to accelerate the age-related loss of muscle mass and strength, predisposing to disability and metabolic disease. Mechanisms underlying disuse and/or inactivity-related muscle deterioration in the older adults, whilst multifaceted, ultimately manifest in an imbalance between rates of muscle protein synthesis and breakdown, resulting in net muscle loss. To date, the most potent intervention to mitigate disuse-induced muscle deterioration is mechanical loading in the form of resistance exercise. However, the feasibility of older individuals performing resistance exercise during disuse and inactivity has been questioned, particularly as illness and injury may affect adherence and safety, as well as accessibility to appropriate equipment and physical therapists. Therefore, optimising nutritional intake during disuse events, through the introduction of protein-rich whole-foods, isolated proteins and nutrient compounds with purported pro-anabolic and anti-catabolic properties could offset impairments in muscle protein turnover and, ultimately, the degree of muscle atrophy and recovery upon re-ambulation. The current review therefore aims to provide an overview of nutritional countermeasures to disuse atrophy and anabolic resistance in older individuals.

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