Differential Gene Expression in Cell Types of the Human Skeletal Muscle: A Bioinformatics-Based Meta-Review

( Kyung-wan Baek ),( So-jeong Kim ),( Ji-seok Kim ),( Sun-ok Kwon ) 한국운동생리학회 2021 운동과학 Vol.30 No.4

PURPOSE: This study evaluates the differences in the expression of genes frequently analyzed in the field of exercise science between the skeletal muscle tissue and various cell types that comprise the skeletal muscle tissue. METHODS: We summarized the genes and proteins expressed in the skeletal muscle that were published in “Exercise Science” journal from 2015 to present. Thereafter, we selected 15 genes and proteins that were the most analyzed genes and proteins in the skeletal muscle. These genes and proteins were horizontally compared for expression differences in skeletal muscle components and cultured cells based on NCBI Gene Expression Omnibus DataSets. RESULTS: The most analyzed genes (encoding analyzed proteins) in skeletal muscle tissues in “Exercise Science” were PPARGC1A, PPARD, MTOR, MAP1LC3A, MAP1LC3B, PRKAA1, AKT1, SLC2A4, MAPK1, COX4I1, MAPK14, MEF2A, MAPK8, RPS6KB1, and SOD1. Among them, PPARGC1A, AKT1, SLC2A4, MAPK1, and COX4I1 were specifically expressed in the skeletal muscle. However, expression of other genes was found to be significantly affected in other cell types of the skeletal muscle tissue. CONCLUSIONS: Genes such as PPARGC1A, which are specifically expressed in the skeletal muscle, may be analyzed without pretreating (such as perfusion) the skeletal muscle tissue. However, expression of other genes may depend on the skeletal muscle cell type. Thus, in such instances, pretreatment, such as perfusion and isolation, should be considered.

MondoA Is Required for Normal Myogenesis and Regulation of the Skeletal Muscle Glycogen Content in Mice

Hui Ran,Yao Lu,Qi Zhang,Qiuyue Hu,Junmei Zhao,Kai Wang,Xuemei Tong,Qing Su 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.3

Background: Skeletal muscle is the largest tissue in the human body, and it plays a major role in exerting force and maintaining metabolism homeostasis. The role of muscle transcription factors in the regulation of metabolism is not fully understood. MondoA is a glucose-sensing transcription factor that is highly expressed in skeletal muscle. Previous studies suggest that MondoA can influence systemic metabolism homeostasis. However, the function of MondoA in the skeletal muscle remains unclear. Methods: We generated muscle-specific MondoA knockout (MAKO) mice and analyzed the skeletal muscle morphology and glycogen content. Along with skeletal muscle from MAKO mice, C2C12 myocytes transfected with small interfering RNA against MondoA were also used to investigate the role and potential mechanism of MondoA in the development and glycogen metabolism of skeletal muscle. Results: MAKO caused muscle fiber atrophy, reduced the proportion of type II fibers compared to type I fibers, and increased the muscle glycogen level. MondoA knockdown inhibited myoblast proliferation, migration, and differentiation by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Further mechanistic experiments revealed that the increased muscle glycogen in MAKO mice was caused by thioredoxin-interacting protein (TXNIP) downregulation, which led to upregulation of glucose transporter 4 (GLUT4), potentially increasing glucose uptake. Conclusion: MondoA appears to mediate mouse myofiber development, and MondoA decreases the muscle glycogen level. The findings indicate the potential function of MondoA in skeletal muscle, linking the glucose-related transcription factor to myogenesis and skeletal myofiber glycogen metabolism.

Potential role of exercise-induced glucose-6-phosphate isomerase in skeletal muscle function

곽성은,신형은,Didi Zhang,이지현,윤경진,배준현,문효열,송욱 한국운동영양학회 2019 Physical Activity and Nutrition (Phys Act Nutr) Vol.23 No.2

[Purpose] Recent studies have shown that glucose-6-phosphate isomerase (GPI)—which is a glycolysis interconversion enzyme—reduces oxidative stress. However, these studies are limited to tumors such as fibrosarcoma, and there are no studies that have examined the effects of exercise on GPI expression in mice skeletal muscle. Furthermore, GPI acts in an autocrine manner thorough its receptor, autocrine motility factor receptor (AMFR); therefore, we investigated expression level changes of secreted GPI from skeletal muscle in in vitro study to examine the potential role of GPI on skeletal muscle. [Methods] First, we performed an in vitro study, to identify the condition that upregulates GPI levels in skeletal muscle cells; we treated C2C12 muscle cells with an exercise-mimicking chemical, AICAR. AICAR treatment upregulated GPI expression level in C2C12 cell and its secretomes. To confirm the direct effect of GPI on skeletal muscle cells, we treated C2C12 cells with GPI recombinant protein. [Results] We found that GPI improved the viability of C2C12 cells. In the in vivo study, the exercise-treated mice group showed upregulated GPI expression in skeletal muscle. Based on the in vitro study results, we speculated that expression level of GPI in skeletal muscle might be associated with muscle function. We analyzed the association between GPI expression level and the grip strength of the all mice group. The mice group’s grip strengths were upregulated after 2 weeks of treadmill exercise, and GPI expression level positively correlated with the grip strength. [Conclusion] These results suggested that the exercise-induced GPI expression in skeletal muscle might have a positive effect on skeletal muscle function.

Resistance exercise: a mighty tool that adapts, destroys, rebuilds and modulates the molecular and structural environment of skeletal muscle

Käthe Bersiner,박소영,Kirill Schaaf,양우휘,Christian Theis,Daniel Jacko,Sebastian Gehlert 한국운동영양학회 2023 Physical Activity and Nutrition (Phys Act Nutr) Vol.27 No.2

[Purpose] Skeletal muscle regulates health and performance by maintaining or increasing strength and muscle mass. Although the molecular mechanisms in response to resistance exercise (RE) significantly target the activation of protein synthesis, a plethora of other mechanisms and structures must be involved in orchestrating the communication, repair, and restoration of homeostasis after RE stimulation. In practice, RE can be modulated by variations in intensity, continuity and volume, which affect molecular responses and skeletal muscle adaptation. Knowledge of these aspects is important with respect to planning of training programs and assessing the impact of RE training on skeletal muscle. [Methods] In this narrative review, we introduce general aspects of skeletal muscle substructures that adapt in response to RE. We further highlighted the molecular mechanisms that control human skeletal muscle anabolism, degradation, repair and memory in response to acute and repeated RE and linked these aspects to major training variables. [Results] Although RE is a key stimulus for the activation of skeletal muscle anabolism, it also induces myofibrillar damage. Nevertheless, to increase muscle mass accompanied by a corresponding adaptation of the essential substructures of the sarcomeric environment, RE must be continuously repeated. This requires the permanent engagement of molecular mechanisms that re-establish skeletal muscle integrity after each RE–induced muscle damage. [Conclusion] Various molecular regulators coordinately control the adaptation of skeletal muscle after acute and repeated RE and expand their actions far beyond muscle growth. Variations of key resistance training variables likely affect these mechanisms without affecting muscle growth.

골격근 미토콘드리아와 인슐린저항성: 운동의 역할

곽효범 ( Hyo Bum Kwak ) 대한비만학회 2015 The Korean journal of obesity Vol.24 No.2

골격근, 간, β-세포, 지방세포, 위장, α-세포, 신장 그리고 뇌에서의 인슐린저항성은 비만 및 제2형 당뇨병 유발의 중요한 요인들이다. 이중에서 체중의 40-50%를 차지하고 있는 골격근의 인슐린저항성은 골격근 안으로의 포도당 흡수를 감소시킨다. 많은 선행연구들에 의하면 제2형 당뇨병 환자나 인슐린저항성이 있는 비만한 환자들은 정상인에 비해 골격근 내 적은 미토콘드리아가 존재한다고 보고되고 있다. 하지만 골격근 내 미토콘드리아가 인슐린저항성을 유발하는 원인인지에 대해서는 많은 논쟁이 되고 있다. 먼저 골격근의 인슐린저항성이 미토콘드리아의 기능장애와 관련되어 있다는 주장은 다음과 같은 가설에 근거하고 있다. 1) 비만 또는 제2형 당뇨병은 골격근의 지방산화 능력을 감소시키고 인슐린저항성을 유발하는 지방형성 중간물질들(예, FA-CoA, DAG, ceramide)의 축적을 증가시킨다. 2) 비만 또는 고지방섭취에 의한 인슐린저항성은 골격근 내 미토콘드리아의 과부하와 불완전한 지방산화에 의해 야기된다. 3) 골격근 내 미토콘드리아에서 생성된 산화적 스트레스(예, H2O2)가 비만 및 고지방섭취에 의한 인슐린저항성을 유발한다. 하지만 골격근 내 미토콘드리아의 기능장 애는 인슐린저항성을 유발하지 않는다는 상반된 주장도 다음과 같은 이유로 제기되고 있다. 1) 고지방섭취 동물은 인슐린저항성 유발뿐만 아니라 골격근 내 미토콘드리아의 증가도 야기한다. 2) 제2형 당뇨병과 인슐린저항성이 있는 비만한 환자들은 정상인에 비해 높은 골격근 지방산화능력을 나타낸다. 그러나 여러 가지 형태의 운동(일회성vs. 장기간, 유산소 vs. 저항성)은 비만과 제2형 당뇨병에 의해 야기되는 인슐린저항성을 처치하고 예방하는데 매우 중요한 역할을 한다. Insulin resistance in skeletal muscle, liver, β-cells, fat cells, the gastrointestinal track, α-cells, kidneys, and brain represents the core defect in obesity or type 2 diabetes (T2D). Among them, skeletal muscle insulin resistance due to obesity or T2D is manifested by decreased glucose uptake because skeletal muscle comprises 40-50% of the total human body mass. Many previous reports indicate that T2D patients or obese insulinresistant individuals have less mitochondria in their skeletal muscles than lean control subjects. Whether or not mitochondria in skeletal muscle play a causal role in insulin resistance has been debated. A large number of studies demonstrated that skeletal muscle insulin resistance is associated with mitochondrial deficiency including 1) reduced fatty acid oxidation and increased accumulation of lipid intermediates (e.g., FA-CoA, DAG, ceramide), 2) increased mitochondrial overload and incomplete fatty acid oxidation, and 3) increased mitochondrial oxidative stress (e.g., H2O2) in skeletal muscle. In contrast, some studies demonstrated that mitochondrial dysfunction in skeletal muscle is not responsible for insulin resistance, suggesting that 1) the development of insulin resistance in high-fat diet animals occurs with increased muscle mitochondria, and 2) fatty acid oxidation is higher in T2D patients and obese insulin-resistant individuals compared with lean control subjects. However, various types of exercises (acute vs chronic, aerobic vs resistance) are critical in the treatment and prevention of insulin resistance in obesity and T2D.

Human Tissue-Engineered Skeletal Muscle: A Tool for Metabolic Research

김지훈,유승민,손장원 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.3

Skeletal muscle is now regarded as an endocrine organ based on its secretion of myokines and exerkines, which, in response to metabolic stimuli, regulate the crosstalk between the skeletal muscle and other metabolic organs in terms of systemic energy homeostasis. This conceptual basis of skeletal muscle as a metabolically active organ has provided insights into the potential role of physical inactivity and conditions altering muscle quality and quantity in the development of multiple metabolic disorders, including insulin resistance, obesity, and diabetes. Therefore, it is important to understand human muscle physiology more deeply in relation to the pathophysiology of metabolic diseases. Since monolayer cell lines or animal models used in conventional research differ from the pathophysiological features of the human body, there is increasing need for more physiologically relevant in vitro models of human skeletal muscle. Here, we introduce recent studies on in vitro models of human skeletal muscle generated from adult myogenic progenitors or pluripotent stem cells and summarize recent progress in the development of three-dimensional (3D) bioartificial muscle,which mimics the physiological complexity of native skeletal muscle tissue in terms of maturation and functionality. We then discussthe future of skeletal muscle 3D-organoid culture technology in the field of metabolic research for studying pathological mechanisms and developing personalized therapeutic strategies.

Acupuncture Muscle Channel in the Subcutaneous Layer of Rat Skin

Kwang-Sup Soh,Byung-Cheon Lee,Vyacheslav Ogay,Yuwon Lee,Jin-Kyu Lee,Ki Woo Kim 사단법인약침학회 2008 Journal of Acupuncture & Meridian Studies Vol.1 No.1

Using a mixed-dye injection technique, we found a novel kind of muscle fiber with a lumen, established its precise location in the subcutaneous muscle layer along the acupuncture muscle of the bladder line, and determined its detailed ultrastructure. The channels with flowing liquid were a novel kind of muscle fibers with lumens and they were located in the subcutaneous muscle layer of rat. Their detection was realized by using chrome-hematoxylin and a mixture of fluorescent nanoparticles and commercial Pelikan ink. These acupuncture muscle channels were hidden among the neighboring skin skeletal muscle fibers and were barely distinguishable from them with light microscopes. Only with a transmission electron microscope were their characteristic features shown to be different from normal skin skeletal muscle. These features included undifferentiated muscle fibers that resembled immature myofibrils without Z-lines and reassembled telophase nuclei. Using a mixed-dye injection technique, we found a novel kind of muscle fiber with a lumen, established its precise location in the subcutaneous muscle layer along the acupuncture muscle of the bladder line, and determined its detailed ultrastructure. The channels with flowing liquid were a novel kind of muscle fibers with lumens and they were located in the subcutaneous muscle layer of rat. Their detection was realized by using chrome-hematoxylin and a mixture of fluorescent nanoparticles and commercial Pelikan ink. These acupuncture muscle channels were hidden among the neighboring skin skeletal muscle fibers and were barely distinguishable from them with light microscopes. Only with a transmission electron microscope were their characteristic features shown to be different from normal skin skeletal muscle. These features included undifferentiated muscle fibers that resembled immature myofibrils without Z-lines and reassembled telophase nuclei.

Contrast Enhanced Ultrasound Perfusion Imaging in Skeletal Muscle

TheAnh Nguyen,Brian P. Davidson 한국심초음파학회 2019 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.27 No.3

The ability to accurately evaluate skeletal muscle microvascular blood flow has broad clinical applications for understanding the regulation of skeletal muscle perfusion in health and disease states. Contrast-enhanced ultrasound (CEU) perfusion imaging, a technique originally developed to evaluate myocardial perfusion, is one of many techniques that have been applied to evaluate skeletal muscle perfusion. Among the advantages of CEU perfusion imaging of skeletal muscle is that it is rapid, safe and performed with equipment already present in most vascular medicine laboratories. The aim of this review is to discuss the use of CEU perfusion imaging in skeletal muscle. This article provides details of the protocols for CEU imaging in skeletal muscle, including two predominant methods for bolus and continuous infusion destruction-replenishment techniques. The importance of stress perfusion imaging will be highlighted, including a discussion of the methods used to produce hyperemic skeletal muscle blood flow. A broad overview of the disease states that have been studied in humans using CEU perfusion imaging of skeletal muscle will be presented including: (1) peripheral arterial disease; (2) sickle cell disease; (3) diabetes; and (4) heart failure. Finally, future applications of CEU imaging in skeletal muscle including therapeutic CEU imaging will be discussed along with technological developments needed to advance the field.

Aerobic exercise prevents apoptosis in skeletal muscles of high-fat-fed ovariectomized rats

김혜진,권오란 한국운동영양학회 2022 Physical Activity and Nutrition (Phys Act Nutr) Vol.26 No.2

[Purpose] Aging and obesity are associated with skeletal muscle atrophy-related signaling pathways, including apoptosis. Many studies have shown that menopause is associated with an increased risk of skeletal muscle atrophy. There is an increasing need to develop strategies that will improve the risk of skeletal muscle atrophy through exercise interventions. However, the effect of exercise on estrogen deficiency-induced apoptosis in skeletal muscles is poorly understood. Therefore, we examined the effects of low-intensity exercise on ovariectomy (OVX)-induced apoptosis of the soleus and plantaris muscles. [Methods] The ovaries of all female Sprague-Dawley rats aged 8 weeks, were surgically removed to induce postmenopausal status. The rats were randomly divided into three treatment groups: (1) NSV (normal-diet- sedentary-OVX); (2) HSV (high-fat-diet-sedentary-OVX); and (3) HEV (high-fat-diet-exercise-OVX). The exercise groups were regularly running for 30-40 min/day at 15- 18 m/minute, five times/week, for eight weeks. [Results] The mRNA levels of Bax significantly decreased in the exercised soleus muscle, and caspase-3 decreased in the plantaris. The skeletal muscle TUNEL-positive apoptotic cells in the high-fat-diet-sedentary OVX rats improved in the treadmill exercise group. Additionally, nuclear caspase-3 levels decreased in the treadmill exercise group compared to those in both sedentary groups. These results suggest that low-intensity treadmill exercise prevents skeletal muscle apoptosis in HFD-fed OVX rats. [Conclusion] Induction of HFD in estrogen-deficient mice increased apoptosis in skeletal muscle, which could also be alleviated by low-intensity aerobic exercise. These results may indicate a crucial therapeutic effect of treadmill exercise in preventing skeletal muscle apoptosis in menopausal or post-menopausal women.

Treadmill exercise ameliorates the regulation of energy metabolism in skeletal muscle of NSE/PS2m-transgenic mice with Alzheimer`s disease

( Jang-soo Yook ),( Joon-yong Cho ) 한국운동영양학회 2017 Physical Activity and Nutrition (Phys Act Nutr) Vol.21 No.1

[Purpose] Alzheimer`s disease (AD) is classified as a progressive neurological disorder, which not only causes cognitive impairment but also abnormal weight loss, with a reduction of muscle mass related to the accumulation of amyloid-β (Aβ) in skeletal muscle. Thus, we investigated the effect of treadmill exercise on Aβ deposition, and p-AMPK, p-ACC, BDNF, and GLUT4 protein levels the regulation of muscle energy metabolism using an AD mouse. [Methods] At 13 months of age, NSE/PS2m mice (Tg) and control mice (non-Tg) were assigned to non-exercise control (Con) and exercise groups (Exe). The four groups were as follows: non-Tg Con, non-Tg Exe, Tg Con, and Tg Exe. The treadmill exercise was carried out for 12 weeks. [Results] The highest levels of Aβ expression in the skeletal muscle were in the Tg Con group. Aβ expression was significantly reduced in the Tg Exe group, compared to the Tg Con group. Congo red staining showed remarkable diffuse red amyloid deposition in the Tg Con group, while Aβ-deposition in the skeletal was reduced with muscle exercise in the Tg Exe group. Exercise also increased AMPK and ACC phosphorylation and BDNF and GLUT4 expression in the skeletal muscle of non-Tg and Tg mice. [Conclusion] Treadmill exercise reduces Aβ-deposition in the skeletal muscle and improves the regulation of energy metabolism. Thus, collectively, these results suggest that exercise could be a positive therapeutic strategy for skeletal muscle dysfunction in AD patients.