• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.573-582
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• 2023

Muscle atrophy is characterized by the loss of muscle function. Many efforts are being made to prevent muscle atrophy, and exercise is an important alternative. Methylglyoxal is a well-known causative agent of metabolic diseases and diabetic complications. This study aimed to evaluate whether methylglyoxal induces muscle atrophy and to evaluate the ameliorative effect of moderate-intensity aerobic exercise in a methylglyoxal-induced muscle atrophy animal model. Each mouse was randomly divided into three groups: control, methylglyoxal-treated, and methylglyoxal-treated within aerobic exercise. In the exercise group, each mouse was trained on a treadmill for 2 weeks. On the last day, all groups were evaluated for several atrophic behaviors and skeletal muscles, including the soleus, plantaris, gastrocnemius, and extensor digitorum longus were analyzed. In the exercise group, muscle mass was restored, causing in attenuation of muscle atrophy. The gastrocnemius and extensor digitorum longus muscles showed improved fiber cross-sectional area and reduced myofibrils. Further, they produced regulated atrophy-related proteins (i.e., muscle atrophy F-box, muscle RING-finger protein-1, and myosin heavy chain), indicating that aerobic exercise stimulated their muscle sensitivity to reverse skeletal muscle atrophy. In conclusion, shortness of the gastrocnemius caused by methylglyoxal may induce the dynamic imbalance of skeletal muscle atrophy, thus methylglyoxal may be a key target for treating skeletal muscle atrophy. To this end, aerobic exercise may be a powerful tool for regulating methylglyoxal-induced skeletal muscle atrophy.

• Perspectives in Nursing Science
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• v.2 no.1
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• pp.19-36
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• 2005

Muscle atrophy is defined as a decrease in muscle mass, cross-sectional area, and myofibrillar protein content. Causes inducing muscle atrophy may be inactivity, denervation, undernutrition and steroid. Inactivity may decrease protein synthesis and increase protein breakdown of skeletal muscle. The muscle atrophy due to inactivity was induced by bed rest, hindlimb suspension, cast, total hip replacement arthroplasty, anterior cruciate ligament reconstruction. Denervated atrophy may be induced by the loss of innervation from lower motor neuron. The atrophy was apparent in the lower limb of hemiplegic patients following ischemic stroke and in the hindlimb of ischemic stroke rats. Protein breakdown of skeletal muscle in the undernourished state results in muscle atrophy. The atrophy due to undernutrition was evident in cancer and leukemia patients and in the undernourished rats. Steroids have been used to treat allergies, inflammatory diseases, autoimmune diseases and to inhibit immune function following transplantation. Steroids may induce muscle atrophy by protein breakdown of skeletal muscle. Muscle Physiology Laboratoryat College of Nursing, Seoul National University proved that dexamethasone may induce hindlimb muscle atrophy in rats and exercise and DHEA may attenuate hindlimb muscle atrophy induced by the steroid in rats. Nurses working with patients undergoing steroid treatment need to be cognizant of steroid induced muscle atrophy. They need to assess whether muscle atrophy is being occurred during and after the steroid treatment. Moreover, they need to apply exercise and DHEA to the patients undergoing steroid treatment in order to attenuate the steroid induced muscle atrophy.

• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.495-505
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• 2024

Gromwell (Lithospermum erythrorhizon, LE) can mitigate obesity-induced skeletal muscle atrophy in C2C12 myotubes and high-fat diet (HFD)-induced obese mice. The purpose of this study was to investigate the anti-skeletal muscle atrophy effects of LE and the underlying molecular mechanism. C2C12 myotubes were pretreated with LE or shikonin, and active component of LE, for 24 h and then treated with 500 μM palmitic acid (PA) for an additional 24 h. Additionally, mice were fed a HFD for 8 weeks to induced obesity, and then fed either the same diet or a version containing 0.25% LE for 10 weeks. LE attenuated PA-induced myotubes atrophy in differentiated C2C12 myotubes. The supplementation of LE to obese mice significantly increased skeletal muscle weight, lean body mass, muscle strength, and exercise performance compared with those in the HFD group. LE supplementation not only suppressed obesity-induced skeletal muscle lipid accumulation, but also downregulated TNF-α and atrophic genes. LE increased protein synthesis in the skeletal muscle via the mTOR pathway. We observed LE induced increase of mitochondrial biogenesis and upregulation of oxidative phosphorylation related genes in the skeletal muscles. Furthermore, LE increased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and the phosphorylation of adenosine monophosphate-activated protein kinase. Collectively, LE may be useful in ameliorating the detrimental effects of obesity-induced skeletal muscle atrophy through the increase of protein synthesis and mitochondrial biogenesis of skeletal muscle.

• Korean Journal of Exercise Nutrition
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• v.23 no.3
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• pp.45-49
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• 2019

[Purpose] Recent studies suggest that ursolic acid (UA) is a potential candidate for a resistance exercise mimetic that can increase muscle mass and alleviate the deleterious effect of skeletal muscle atrophy on bone health. However, these studies evaluated the effects of UA on skeletal muscle and bone tissues, and they have not verified whether such effect could occur concurrently on muscle and bone, as is the case with resistance exercise. Thus, the aim of this study was to analyze the effect of UA injection on muscle mass and bone microstructure using an animal model of atrophy to demonstrate the potential of UA as a resistance exercise mimetic. [Methods] The immobilization (IM) method was used on the left hindlimb of Sprague Dawley (SD) rats for 10 days to induce muscle atrophy, whereas the right hindlimb was used as an internal control (IC). The animal models were divided into two groups, SED (sedentary, n=6) and UA (n=6) to demonstrate the effect of UA on atrophic skeletal muscles. The UA group received a daily intraperitoneal injection of UA (5 mg/kg/day) for 8 weeks. After 10 days of IM, the data collected for the IC were compared with that of IM to determine whether muscle atrophy might occur. [Results] Muscle atrophy was induced and bone mineral density (BMD) decreased significantly. The 8-week UA treatment significantly increased the gastrocnemius muscle mass compared to the SED group. In regard to the effect of UA on bones, negative results such as a decrease in BMD, trabecular bone volume fraction, and trabecular number, and an increase in trabecular separation, were observed in the SED group, but no such difference was observed in the UA group. No significant difference was observed in atrophic hindlimbs between SED and UA groups. [Conclusion] These results alone are insufficient to suggest that UA is a potential resistance exercise mimetic for atrophic skeletal muscle and weakened bone. However, this study will help determine the potential of UA as a resistance exercise mimetic.

• Herbal Formula Science
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• v.24 no.3
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• pp.153-161
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• 2016

Chronic alcoholic myopathy is one of the most common skeletal muscle disorders. It is characterized by a reduction in the entire skeletal musculature, skeletal muscle weakness, and difficulties in gait. Patients with alcoholic hepatitis and cirrhosis have severe muscle loss that contributes to worsening outcome. Although the myopathy selectively affects Type II (fast twitch, glycolytic, anaerobic) skeletal muscle fibers, total skeletal musculature is reduced. The severity of the muscle atrophy is proportional to the duration and amount of alcohol consumed and leads to decreased muscle strength. The mechanisms for the myopathy are generally unknown but it is not due to overt nutritional deficiency, nor due to either neuropathy or severe liver disease. Skeletal muscle mass and protein content are maintained by a balance between protein synthesis and breakdown and in vivo animal models studies have shown that ethanol inhibits skeletal muscle protein synthesis. Daekumeumja is a traditional Korean medicine that is widely employed to treat various alcohol-induced diseases. Muscle diseases are often related to liver diseases and conditions. The main objective of this study was to assess that Daekumeumja extract could have protective effect against alcoholic myopathy in a Sprague-Dawley rat model. Rats were orally given 25% ethanol (5ml/kg, body weight) for 8 weeks. After 30 minutes, rats were administrated with Daekumeumja extract. Controls were similarly administrated with the vehicle alone. The weights of gastrocnemius, soleus and plantaris muscles were assessed and the morphologic changes of gastrocnemius and plantaris muscles were also assessed by hematoxylin and eosin staining. In results, The muscles from ethanol treated rats displayed a significant reduction in muscle weight and average cross section area compared to Normal group. Daekumeumja extract treated group showed increased muscle weight and muscle fiber compared to the ethanol treated group. It was concluded that Daekumeumja extract showed ameliorating effects on chronic alcohol myopathy in skeletal muscle.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.270-279
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• 2024

Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.454-463
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• 2022

Background: Gintonin-enriched fraction (GEF), a non-saponin fraction of ginseng, is a novel glycolipoprotein rich in hydrophobic amino acids. GEF has recently been shown to regulate lipid metabolism and browning in adipocytes; however, the mechanisms underlying its effects on energy metabolism and whether it affects sarcopenic obesity are unclear. We aimed to evaluate the effects of GEF on skeletal muscle atrophy in high-fat diet (HFD)-induced obese mice. Methods: To examine the effect of GEF on sarcopenic obesity, 4-week-old male ICR mice were used. The mice were divided into four groups: chow diet (CD), HFD, HFD supplemented with 50 mg/kg/day GEF, or 150 mg/kg/day GEF for 6 weeks. We analyzed body mass gain and grip strength, histological staining, western blot analysis, and immunofluorescence to quantify changes in sarcopenic obesity-related factors. Results: GEF inhibited body mass gain while HFD-fed mice gained 22.7 ± 2.0 g, whereas GEF-treated mice gained 14.3 ± 1.2 g for GEF50 and 11.8 ± 1.6 g for GEF150 by downregulating adipogenesis and inducing lipolysis and browning in white adipose tissue (WAT). GEF also enhanced mitochondrial biogenesis threefold in skeletal muscle. Furthermore, GEF-treated skeletal muscle exhibited decreased expression of muscle-specific atrophic genes, and promoted myogenic differentiation and increased muscle mass and strength in a dose-dependent manner (p < 0.05). Conclusion: These findings indicate that GEF may have potential uses in preventing sarcopenic obesity by promoting energy expenditure and attenuating skeletal muscle atrophy.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.491-496
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• 2009

Skeletal muscle atrophy is a common phenomenon during the prolonged muscle disuse caused by cast immobilization, extended aging states, bed rest, space flight, or other factors. However, the cellular mechanisms of the atrophic process are poorly understood. In this study, we investigated the involvement of mitogen-activated protein kinase (MAPK) in the expression of muscle-specific RING finger 1 (MuRF1) during atrophy of the rat gastrocnemius muscle. Histological analysis revealed that cast immobilization induced the atrophy of the gastrocnemius muscle, with diminution of muscle weight and cross-sectional area after 14 days. Cast immobilization significantly elevated the expression of MuRF1 and the phosphorylation of p38 MAPK. The starvation of L6 rat skeletal myoblasts under serum-free conditions induced the phosphorylation of p38 MAPK and the characteristics typical of cast-immobilized gastrocnemius muscle. The expression of MuRF1 was also elevated in serum-starved L6 myoblasts, but was significantly attenuated by SB203580, an inhibitor of p38 MAPK. Changes in the sizes of L6 myoblasts in response to starvation were also reversed by their transfection with MuRF1 small interfering RNA or treatment with SB203580. From these results, we suggest that the expression of MuRF1 in cast-immobilized atrophy is regulated by p38 MAPK in rat gastrocnemius muscles.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.52-58
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• 2024

Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

• Nutrition Research and Practice
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• v.18 no.4
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• pp.451-463
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• 2024

BACKGROUND/OBJECTIVES: The umami taste receptor (TAS1R1/TAS1R3) is endogenously expressed in skeletal muscle and is involved in myogenesis; however, there is a lack of evidence about whether the expression of the umami taste receptor is involved in muscular diseases. This study aimed to elucidate the effects of the umami taste receptor and its mechanism on muscle wasting in cancer cachexia using in vivo and in vitro models. MATERIALS/METHODS: The Lewis lung carcinoma-induced cancer cachexia model was used in vivo and in vitro, and the expressions of umami taste receptor and muscle atrophy-related markers, muscle atrophy F-box protein, and muscle RING-finger protein-1 were analyzed. RESULTS: Results showed that TAS1R1 was significantly downregulated in vivo and in vitro under the muscle wasting condition. Moreover, overexpression of TAS1R1 in vitro in the human primary cell model protected the cells from muscle atrophy, and knockdown of TAS1R1 using siRNA exacerbated muscle atrophy. CONCLUSION: Taken together, the umami taste receptor exerts protective effects on muscle-wasting conditions by restoring dysregulated muscle atrophy in cancer cachexia. In conclusion, this result provided evidence that the umami taste receptor exerts a therapeutic anti-cancer cachexia effect by restoring muscle atrophy.