scholarly journals Maslinic Acid Attenuates Denervation-Induced Loss of Skeletal Muscle Mass and Strength

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2950
Author(s):  
Yuki Yamauchi ◽  
Farhana Ferdousi ◽  
Satoshi Fukumitsu ◽  
Hiroko Isoda
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Gastrocnemius Muscle ◽  
Muscular Atrophy ◽  
Control Diet ◽  
Gene Set Enrichment Analysis ◽  
Pentacyclic Triterpene ◽  
Maslinic Acid

Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults; however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength and to explore the underlying molecular mechanism. Mice were fed either a control diet or a 0.27% MA diet. One week after intervention, the sciatic nerves of both legs were cut to induce muscle atrophy. Mice were examined 14 days after denervation. MA prevented the denervation-induced reduction in gastrocnemius muscle mass and skeletal muscle strength. Microarray gene expression profiling in gastrocnemius muscle demonstrated several potential mechanisms for muscle maintenance. Gene set enrichment analysis (GSEA) revealed different enriched biological processes, such as myogenesis, PI3/AKT/mTOR signaling, TNFα signaling via NF-κB, and TGF-β signaling in MA-treated mice. In addition, qPCR data showed that MA induced Igf1 expression and suppressed the expressions of Atrogin-1, Murf1 and Tgfb. Altogether, our results suggest the potential of MA as a new therapeutic and preventive dietary ingredient for muscular atrophy and strength.

Maslinic acid activates mTORC1 and human TGR5 and induces skeletal muscle hypertrophy

2021 ◽  
Author(s):  
Shotaro Murata ◽  
Takashi Sasaki ◽  
Yuki Yamauchi ◽  
Makoto Shimizu ◽  
Ryuichiro Sato
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Mammalian Target Of Rapamycin ◽  
Standard Diet ◽  
Muscular Hypertrophy ◽  
Akt Inhibitor ◽  
Pentacyclic Triterpene ◽  
Maslinic Acid ◽  
C2c12 Skeletal Muscle Cells

ABSTRACT Maslinic acid, a naturally occurring pentacyclic triterpene in more than 30 plants (including olives), reportedly increases human muscle mass and muscle strength; however, the underlying molecular mechanism remains unknown. C57BL/6J mice were fed a standard diet or supplemented with 0.27% maslinic acid for 4 weeks, and their skeletal muscle mass was measured. Mice that consumed maslinic acid displayed significant increases in gastrocnemius and soleus muscle mass. Cultured mouse-C2C12 skeletal muscle cells were treated with mammalian target of rapamycin complex 1 (mTORC1) or protein kinase b (Akt) inhibitor, and protein synthesis was quantified. Maslinic acid accelerated protein synthesis via mTORC1 activation independent of Akt. Furthermore, maslinic acid activated human Takeda G protein-coupled receptor 5 (TGR5) more strongly than mouse TGR5, augmenting the expression of several genes related to muscular hypertrophy. Maslinic acid activated mTORC1 and human TGR5, implying its contribution to human muscular hypertrophy through these effects.

scholarly journals Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

2020 ◽  
Vol 21 (5) ◽  
pp. 1628 ◽  
Author(s):  
Keisuke Hitachi ◽  
Masashi Nakatani ◽  
Shiori Funasaki ◽  
Ikumi Hijikata ◽  
Mizuki Maekawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Muscle Size ◽  
Skeletal Muscle Atrophy ◽  
Myostatin Gene ◽  
Expression Levels ◽  
Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

scholarly journals Soluble Whey Protein Hydrolysate Ameliorates Muscle Atrophy Induced by Immobilization via Regulating the PI3K/Akt Pathway in C57BL/6 Mice

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3362
Author(s):  
Ji Eun Shin ◽  
Seok Jun Park ◽  
Seung Il Ahn ◽  
Se-Young Choung
Keyword(s):  
Skeletal Muscle ◽  
Whey Protein ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Protein Hydrolysate ◽  
Protein Hydrolysates ◽  
Protein Supplementation ◽  
Whey Protein Hydrolysates ◽  
Whey Protein Hydrolysate

Sarcopenia, a loss of skeletal muscle mass and function, is prevalent in older people and associated with functional decline and mortality. Protein supplementation is necessary to maintain skeletal muscle mass and whey protein hydrolysates have the best nutrient quality among food proteins. In the first study, C57BL/6 mice were subjected to immobilization for 1 week to induce muscle atrophy. Then, mice were administered with four different whey protein hydrolysates for 2 weeks with continuous immobilization. Among them, soluble whey protein hydrolysate (WP-S) had the greatest increase in grip strength, muscle weight, and cross-sectional area of muscle fiber than other whey protein hydrolysates. To investigate the molecular mechanism, we conducted another experiment with the same experimental design. WP-S significantly promoted the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway and inhibited the PI3K/Akt/forkhead box O (FoxO) pathway. In addition, it increased myosin heavy chain (MyHC) expression in both the soleus and quadriceps and changed MyHC isoform expressions. In conclusion, WP-S attenuated muscle atrophy induced by immobilization by enhancing the net protein content regulating muscle protein synthesis and degradation. Thus, it is a necessary and probable candidate for developing functional food to prevent sarcopenia.

scholarly journals Passive repetitive stretching increases skeletal muscle mass and myofiber cross-sectional area in senescence-accelerated model mouse

2021 ◽  
Author(s):  
Yumin Wang ◽  
Satoshi Ikeda ◽  
Katsunori Ikoma
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Gastrocnemius Muscle ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Passive Stretching

Abstract Mechanical stimulation has benefits for muscle mass and function. Passive stretching is widely performed in clinical rehabilitation medicine. However, the hypertrophic effects of passive repetitive stretching on senescent skeletal muscles against muscle atrophy remain unknown. We used senescence-accelerated model SAM-P8 mice. The gastrocnemius muscle was passively repetitive stretched by manual ankle dorsiflexion for 15 min, 5 days a week for 2 weeks under deep anesthesia. We examined the effects of passive stretching on muscle mass, myofiber cross-sectional area, muscle fiber type and composition, satellite cell content, mRNA expression of the signaling pathways involved in muscle protein synthesis, muscle-specific ubiquitin ligases, and myogenic regulatory factors. The gastrocnemius muscle weight of the stretched side increased compared with that of the unstretched side. In addition to the increase in muscle mass, muscle fiber cross-sectional area of the stretched side was greater than that of the unstretched side. Passive repetitive stretching significantly increased the mRNA expression level of Akt, p70S6K, 4E-BP1, Myf5, myogenin, MuRF1. Passive repetitive stretching promoted skeletal muscle mass and myofiber cross-sectional area in SAM-P8 mice. These hypertrophic observations are attributable to the stretch-activated signaling pathways involved in protein turnover. These findings are applicable to clinical muscle strengthening and sarcopenia prevention.

scholarly journals Edward F. Adolph Distinguished Lecture. Skeletal muscle atrophy: Multiple pathways leading to a common outcome

2020 ◽  
Vol 129 (2) ◽  
pp. 272-282 ◽  
Author(s):  
Sue C. Bodine
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Single Gene ◽  
Skeletal Muscle Atrophy ◽  
Protein Breakdown ◽  
E3 Ligases ◽  
The Past

Skeletal muscle atrophy continues to be a serious consequence of many diseases and conditions for which there is no treatment. Our understanding of the mechanisms regulating skeletal muscle mass has improved considerably over the past two decades. For many years it was known that skeletal muscle atrophy resulted from an imbalance between protein synthesis and protein breakdown, with the net balance shifting toward protein breakdown. However, the molecular and cellular mechanisms underlying the increased breakdown of myofibrils was unknown. Over the past two decades, numerous reports have identified novel genes and signaling pathways that are upregulated and activated in response to stimuli such as disuse, inflammation, metabolic stress, starvation and others that induce muscle atrophy. This review summarizes the discovery efforts performed in the identification of several pathways involved in the regulation of skeletal muscle mass: the mammalian target of rapamycin (mTORC1) and the ubiquitin proteasome pathway and the E3 ligases, MuRF1 and MAFbx. While muscle atrophy is a common outcome of many diseases, it is doubtful that a single gene or pathway initiates or mediates the breakdown of myofibrils. Interestingly, however, is the observation that upregulation of the E3 ligases, MuRF1 and MAFbx, is a common feature of many divergent atrophy conditions. The challenge for the field of muscle biology is to understand how all of the various molecules, transcription factors, and signaling pathways interact to produce muscle atrophy and to identify the critical factors for intervention.

scholarly journals REDD1 deletion prevents dexamethasone-induced skeletal muscle atrophy

2014 ◽  
Vol 307 (11) ◽  
pp. E983-E993 ◽  
Author(s):  
Florian A. Britto ◽  
Gwenaelle Begue ◽  
Bernadette Rossano ◽  
Aurélie Docquier ◽  
Barbara Vernus ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Tibialis Anterior ◽  
Skeletal Muscle Mass ◽  
Gastrocnemius Muscle ◽  
Mtorc1 Signaling ◽  
Inhibition Of Protein Synthesis ◽  
Stress Dependent

REDD1 (regulated in development and DNA damage response 1) has been proposed to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) during in vitro hypoxia. REDD1 expression is low under basal conditions but is highly increased in response to several catabolic stresses, like hypoxia and glucocorticoids. However, REDD1 function seems to be tissue and stress dependent, and its role in skeletal muscle in vivo has been poorly characterized. Here, we investigated the effect of REDD1 deletion on skeletal muscle mass, protein synthesis, proteolysis, and mTORC1 signaling pathway under basal conditions and after glucocorticoid administration. Whereas skeletal muscle mass and typology were unchanged between wild-type (WT) and REDD1-null mice, oral gavage with dexamethasone (DEX) for 7 days reduced tibialis anterior and gastrocnemius muscle weights as well as tibialis anterior fiber size only in WT. Similarly, REDD1 deletion prevented the inhibition of protein synthesis and mTORC1 activity (assessed by S6, 4E-BP1, and ULK1 phosphorylation) observed in gastrocnemius muscle of WT mice following single DEX administration for 5 h. However, our results suggest that REDD1-mediated inhibition of mTORC1 in skeletal muscle is not related to the modulation of the binding between TSC2 and 14-3-3. In contrast, our data highlight a new mechanism involved in mTORC1 inhibition linking REDD1, Akt, and PRAS40. Altogether, these results demonstrated in vivo that REDD1 is required for glucocorticoid-induced inhibition of protein synthesis via mTORC1 downregulation. Inhibition of REDD1 may thus be a strategy to limit muscle loss in glucocorticoid-mediated atrophy.

scholarly journals Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice

2015 ◽  
Vol 309 (7) ◽  
pp. E651-E662 ◽  
Author(s):  
Tatsuro Egawa ◽  
Ayumi Goto ◽  
Yoshitaka Ohno ◽  
Shingo Yokoyama ◽  
Akihiro Ikuta ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Degradation ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Ubiquitin Proteasome System ◽  
Hindlimb Unloading ◽  
Slow Twitch Muscle ◽  
Ubiquitin Proteasome ◽  
Slow Twitch

AMPK is considered to have a role in regulating skeletal muscle mass. However, there are no studies investigating the function of AMPK in modulating skeletal muscle mass during atrophic conditions. In the present study, we investigated the difference in unloading-associated muscle atrophy and molecular functions in response to 2-wk hindlimb suspension between transgenic mice overexpressing the dominant-negative mutant of AMPK (AMPK-DN) and their wild-type (WT) littermates. Male WT ( n = 24) and AMPK-DN ( n = 24) mice were randomly divided into two groups: an untreated preexperimental control group ( n = 12 in each group) and an unloading ( n = 12 in each group) group. The relative soleus muscle weight and fiber cross-sectional area to body weight were decreased by ∼30% in WT mice by hindlimb unloading and by ∼20% in AMPK-DN mice. There were no changes in puromycin-labeled protein or Akt/70-kDa ribosomal S6 kinase signaling, the indicators of protein synthesis. The expressions of ubiquitinated proteins and muscle RING finger 1 mRNA and protein, markers of the ubiquitin-proteasome system, were increased by hindlimb unloading in WT mice but not in AMPK-DN mice. The expressions of molecules related to the protein degradation system, phosphorylated forkhead box class O3a, inhibitor of κBα, microRNA (miR)-1, and miR-23a, were decreased only in WT mice in response to hindlimb unloading, and 72-kDa heat shock protein expression was higher in AMPK-DN mice than in WT mice. These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system.

Activation of the vasoactive intestinal peptide 2 receptor modulates normal and atrophying skeletal muscle mass and force

2005 ◽  
Vol 98 (2) ◽  
pp. 655-662 ◽  
Author(s):  
Richard T. Hinkle ◽  
Elizabeth Donnelly ◽  
David B. Cody ◽  
Russell J. Sheldon ◽  
Robert J. Isfort
Keyword(s):  
Skeletal Muscle ◽  
Vasoactive Intestinal Peptide ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Skeletal Muscle Atrophy ◽  
Physiological Control ◽  
Corticosteroid Administration ◽  
Skeletal Muscle Wasting ◽  
Selective Agonist

Of the two known vasoactive intestinal peptide receptors (VPAC1R and VPAC2R), the VPAC2R is expressed in skeletal muscle. To evaluate the function of the VPAC2R in the physiological control of skeletal muscle mass, we utilized the VPAC1R selective agonist [K15,R16,L27]VIP(1-7) GRF(8-27)-NH2 and the VPAC2R selective agonist Ro-25-1553 to treat mice and rats undergoing either nerve damage-, corticosteroid-, or disuse-induced skeletal muscle atrophy. These analyses demonstrated that activation of VPAC2R, but not VPAC1R, reduced the loss of skeletal muscle mass and force during conditions of skeletal muscle atrophy resulting from corticosteroid administration, denervation, casting-induced disuse, increased skeletal muscle mass, and force of nonatrophying muscles. These studies indicate that VPAC2R agonists may have utility for the treatment of skeletal muscle-wasting diseases.

scholarly journals Total Antioxidant from Herbal Medicine as a Possible Tool for the Multifunctional Prevention of Muscular Atrophy

2020 ◽  
Author(s):  
Viani Anggi
Keyword(s):  
Skeletal Muscle ◽  
Nervous System ◽  
Herbal Medicine ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscular Atrophy ◽  
Total Antioxidant ◽  
Disease Impact ◽  
The Impact ◽  
Central Sulawesi

Muscular atrophy is one of disease by the loss of skeletal muscle mass. So, by the loss in muscle often causes rapid muscle atrophy and the occurs during injury and illness its causes immobilization in spinal muscle mass. Usually, the impact factor of the nervous system in musculoskeletal is caused by aging, immobility, malnutrition, medication and even the range of injuries disease impact by the nervous system. To meet the needs needed by the loss of skeletal, we need high total antioxidant from herbal medicine as multifunctional potentially prevention of muscular atrophy condition. Antioxidants are agents that can slow down or prevent oxidation process and protect cells system from the damage of cell by the loss skeletal in muscle mass. One of herbal medicine is Abelmoschus manihot L. Medik From Palu of central Sulawesi as a possible multifunctional prevention of Muscular Atrophy, where the total antioxidant value is 3,45 mg/mL.

scholarly journals Swim training affects Akt signaling and ameliorates loss of skeletal muscle mass in a mouse model of amyotrophic lateral sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karol Cieminski ◽  
Damian Jozef Flis ◽  
Katarzyna Dzik ◽  
Jan Jacek Kaczor ◽  
Emilia Czyrko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Tibialis Anterior Muscle ◽  
Akt Signaling ◽  
The Body ◽  
Skeletal Muscle Atrophy ◽  
Akt Signaling Pathway

AbstractWe tested the hypothesis that swim training reverses the impairment of Akt/FOXO3a signaling, ameliorating muscle atrophy in ALS mice. Transgenic male mice B6SJL-Tg (SOD1G93A) 1Gur/J were used as the ALS model (n = 35), with wild-type B6SJL (WT) mice as controls (n = 7). ALS mice were analyzed before ALS onset, at ALS onset, and at terminal ALS. Levels of insulin/Akt signaling pathway proteins were determined, and the body and tibialis anterior muscle mass and plasma creatine kinase. Significantly increased levels of FOXO3a in ALS groups (from about 13 to 21-fold) compared to WT mice were observed. MuRF1 levels in the ONSET untrained group (12.0 ± 1.7 AU) were significantly higher than in WT mice (1.12 ± 0.2 AU) and in the BEFORE ALS group (3.7 ± 0.9 AU). This was associated with body mass and skeletal muscle mass reduction. Swim training significantly ameliorated the reduction of skeletal muscle mass in both TERMINAL groups (p < 0.001) and partially reversed changes in the levels of Akt signaling pathway proteins. These findings shed light on the swimming-induced attenuation of skeletal muscle atrophy in ALS with possible practical implications for anti-cachexia approaches.

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