scholarly journals Roles of Skeletal Muscle-Derived Exosomes in Organ Metabolic and Immunological Communication

2021 ◽  
Vol 12 ◽  
Author(s):  
Wataru Aoi ◽  
Yuko Tanimura

Skeletal muscles secrete various factors, such as proteins/peptides, nucleotides, and metabolites, which are referred to as myokines. Many of these factors are transported into extracellular bodily fluids in a free or protein-bound form. Furthermore, several secretory factors have been shown to be wrapped up by small vesicles, particularly exosomes, secreted into circulation, and subsequently regulate recipient cells. Thus, exosome contents can be recognized as myokines. In recipient cells, proteins, microRNAs, and metabolites in exosomes can regulate the expression and activity of target proteins associated with nutrient metabolism and immune function. The levels of circulating exosomes and their contents are altered in muscle disorders and metabolic-related states, such as metabolic dysfunction, sarcopenia, and physical fitness. Therefore, such circulating factors could mediate various interactions between skeletal muscle and other organs and may be useful as biomarkers reflecting physiological and pathological states associated with muscular function. Here, this review summarizes secretory regulation of muscle-derived exosomes. Their metabolic and immunological roles and the significance of their circulating levels are also discussed.

2020 ◽  
Vol 21 (7) ◽  
pp. 2620 ◽  
Author(s):  
Michel Abou-Samra ◽  
Camille M. Selvais ◽  
Nicolas Dubuisson ◽  
Sonia M. Brichard

Adiponectin (ApN) is a hormone abundantly secreted by adipocytes and it is known to be tightly linked to the metabolic syndrome. It promotes insulin-sensitizing, fat-burning, and anti-atherosclerotic actions, thereby effectively counteracting several metabolic disorders, including type 2 diabetes, obesity, and cardiovascular diseases. ApN is also known today to possess powerful anti-inflammatory/oxidative and pro-myogenic effects on skeletal muscles exposed to acute or chronic inflammation and injury, mainly through AdipoR1 (ApN specific muscle receptor) and AMP-activated protein kinase (AMPK) pathway, but also via T-cadherin. In this review, we will report all the beneficial and protective properties that ApN can exert, specifically on the skeletal muscle as a target tissue. We will highlight its effects and mechanisms of action, first in healthy skeletal muscle including exercised muscle, and second in diseased muscle from a variety of pathological conditions. In the end, we will go over some of AdipoRs agonists that can be easily produced and administered, and which can greatly mimic ApN. These interesting and newly identified molecules could pave the way towards future therapeutic approaches to potentially prevent or combat not only skeletal muscle disorders but also a plethora of other diseases with sterile inflammation or metabolic dysfunction.


2007 ◽  
Vol 103 (4) ◽  
pp. 1412-1418 ◽  
Author(s):  
Marco Testa ◽  
Bianca Rocca ◽  
Lucia Spath ◽  
Franco O. Ranelletti ◽  
Giovanna Petrucci ◽  
...  

Conflicting data have been reported on cyclooxygenase (COX)-1 and COX-2 expression and activity in striated muscles, including skeletal muscles and myocardium, in particular it is still unclear whether muscle cells are able to produce prostaglandins (PGs). We characterized the expression and enzymatic activity of COX-1 and COX-2 in the skeletal muscles and in the myocardium of mice, rats and humans. By RT-PCR, COX-1 and COX-2 mRNAs were observed in homogenates of mouse and rat hearts, and in different types of skeletal muscles from all different species. By Western blotting, COX-1 and -2 proteins were detected in skeletal muscles and hearts from rodents, as well as in skeletal muscles from humans. Immunoperoxidase stains showed that COX-1 and -2 were diffusely expressed in the myocytes of different muscles and in the myocardiocytes from all different species. In the presence of arachidonic acid, which is the COX enzymatic substrate, isolated skeletal muscle and heart samples from rodents released predominantly PGE2. The biosynthesis of PGE2 was reduced between 50 and 80% ( P < 0.05 vs. vehicle) in the presence of either COX-1- or COX-2-selective blockers, demonstrating that both isoforms are enzymatically active. Exogenous PGE2 added to isolated skeletal muscle preparations from rodents did not affect contraction, whereas it significantly fastened relaxation of a slow type muscle, such as soleus. In conclusion, COX-1 and COX-2 are expressed and enzymatically active in myocytes of skeletal muscles and hearts of rodents and humans. PGE2 appears to be the main product of COX activity in striated muscles.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qianghua Xia ◽  
Xubo Huang ◽  
Jieru Huang ◽  
Yongfeng Zheng ◽  
Michael E. March ◽  
...  

Skeletal muscle is the most abundant type of tissue in human body, being involved in diverse activities and maintaining a finely tuned metabolic balance. Autophagy, characterized by the autophagosome–lysosome system with the involvement of evolutionarily conserved autophagy-related genes, is an important catabolic process and plays an essential role in energy generation and consumption, as well as substance turnover processes in skeletal muscles. Autophagy in skeletal muscles is finely tuned under the tight regulation of diverse signaling pathways, and the autophagy pathway has cross-talk with other pathways to form feedback loops under physiological conditions and metabolic stress. Altered autophagy activity characterized by either increased formation of autophagosomes or inhibition of lysosome-autophagosome fusion can lead to pathological cascades, and mutations in autophagy genes and deregulation of autophagy pathways have been identified as one of the major causes for a variety of skeleton muscle disorders. The advancement of multi-omics techniques enables further understanding of the molecular and biochemical mechanisms underlying the role of autophagy in skeletal muscle disorders, which may yield novel therapeutic targets for these disorders.


Author(s):  
S.A. Moiseev

The question of physiological function variability is of great theoretical interest, since it is a part of the theory of human voluntary movement control. The skeletal muscle control system should probably have a mechanism to reduce or limit the range of its possible variations. Presumably, the organization of the motor system elements according to the principle of muscular synergy is of such a nature. The objective of the work is to study variations and signs of the coordinated bioelectric activity of skeletal muscles in one of the resulting archery phases. Materials and Methods. The study enrolled 5 highly qualified sportsmen (Master of Sport, International Master of Sport). Archers shot 10 series of 3 shots, target distance 18 m, indoors. Simultaneous recording of electrical activity of 12 skeletal muscles of the upper limb girdle and a 3D video sequence was made. The authors analyzed indicators of distribution, descriptive and variation statistics for grouped data. Multiple regression analysis was used to identify signs of consistent muscle activity. Results. Variability magnitudes, characterized by statistical parameters, established for the turn-off-peak characteristics of various muscles, did not have an explicit dependence. Muscles with relatively high scattering parameters in terms of the EMG average amplitude could have a small variation in the average number of EMG turns. The radial flexor of the left hand wrist was a part of muscular synergy in 90 % of cases, the anterior part of the left limb deltoid muscle – in 80 % of cases, the lower and upper beams of the right and left cowl muscle – in 70 % of cases. Other muscles under consideration were their part in less than 60 % of cases. Conclusion. The system of skeletal muscles that are actively involved in the resulting phases of precision movement can be controlled according to the mechanism of functional synergy formation, which probably helps to reduce the range of possible variations in the parameters of muscle electroactivity. Keywords: variability, archery, electromyography, coordination structure, muscle synergy. Вопрос вариативности физиологических функций представляет интерес в теоретическом плане, поскольку является частью теории управления произвольными движениями человека. Система управления скелетными мышцами, вероятно, должна иметь механизм, позволяющий сократить или ограничить диапазон возможных ее вариаций. Таковым, предположительно, является организация элементов моторной системы по принципу мышечных синергий. Цель работы – изучение вариаций и признаков согласованной биоэлектрической активности скелетных мышц в одной из результирующих фаз выстрела из лука. Материалы и методы. В исследованиях приняли участие 5 высококвалифицированных спортсменов (МС, МСМК). Лучники выполняли 10 серий по 3 выстрела с дистанции 18 м в крытом помещении. Производилась синхронная регистрация электрической активности 12 скелетных мышц верхнего плечевого пояса и 3D-видеоряда. Анализировались показатели распределения, описательной и вариационной статистики для сгруппированных данных. Для выявления признаков согласованной активности мышц применялся множественный регрессионный анализ. Результаты. Величины вариативности, характеризуемые статистическими параметрами, установленные для турн-аплитудных характеристик различных мышц, не имели явной зависимости. Мышцы, имеющие относительно высокие параметры разброса значений по показателю средней амплитуды ЭМГ, могли иметь небольшую вариативность среднего числа турнов ЭМГ. Лучевой сгибатель кисти левой руки являлся частью мышечной синергии в 90 % случаев, передняя часть дельтовидной мышцы левой конечности – в 80 %, нижние и верхние пучки трапециевидной мышцы правой и левой сторон – в 70 %. Другие исследуемые мышцы являлись их частью в менее чем 60 % случаев. Выводы. Управление системой скелетных мышц, принимающих активное участие в реализации одной из результирующих фаз точностного движения, может осуществляться по механизму образования функциональных синергий, что, вероятно, способствует снижению диапазона возможных вариаций параметров электроактивности мышц. Ключевые слова: вариативность, стрельба из лука, электромиография, координационная структура, мышечные синергии.


2021 ◽  
Vol 12 ◽  
pp. 204173142098133
Author(s):  
Juan M. Fernández-Costa ◽  
Xiomara Fernández-Garibay ◽  
Ferran Velasco-Mallorquí ◽  
Javier Ramón-Azcón

Muscular dystrophies are a group of highly disabling disorders that share degenerative muscle weakness and wasting as common symptoms. To date, there is not an effective cure for these diseases. In the last years, bioengineered tissues have emerged as powerful tools for preclinical studies. In this review, we summarize the recent technological advances in skeletal muscle tissue engineering. We identify several ground-breaking techniques to fabricate in vitro bioartificial muscles. Accumulating evidence shows that scaffold-based tissue engineering provides topographical cues that enhance the viability and maturation of skeletal muscle. Functional bioartificial muscles have been developed using human myoblasts. These tissues accurately responded to electrical and biological stimulation. Moreover, advanced drug screening tools can be fabricated integrating these tissues in electrical stimulation platforms. However, more work introducing patient-derived cells and integrating these tissues in microdevices is needed to promote the clinical translation of bioengineered skeletal muscle as preclinical tools for muscular dystrophies.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anastasia Georgiadi ◽  
Valeria Lopez-Salazar ◽  
Rabih El- Merahbi ◽  
Rhoda Anane Karikari ◽  
Xiaochuan Ma ◽  
...  

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.


2015 ◽  
Vol 308 (6) ◽  
pp. R530-R542 ◽  
Author(s):  
Victoria J. Vieira-Potter ◽  
Jaume Padilla ◽  
Young-Min Park ◽  
Rebecca J. Welly ◽  
Rebecca J. Scroggins ◽  
...  

Ovariectomized rodents model human menopause in that they rapidly gain weight, reduce spontaneous physical activity (SPA), and develop metabolic dysfunction, including insulin resistance. How contrasting aerobic fitness levels impacts ovariectomy (OVX)-associated metabolic dysfunction is not known. Female rats selectively bred for high and low intrinsic aerobic fitness [high-capacity runners (HCR) and low-capacity runners (LCR), respectively] were maintained under sedentary conditions for 39 wk. Midway through the observation period, OVX or sham (SHM) operations were performed providing HCR-SHM, HCR-OVX, LCR-SHM, and LCR-OVX groups. Glucose tolerance, energy expenditure, and SPA were measured before and 4 wk after surgery, while body composition via dual-energy X-ray absorptiometry and adipose tissue distribution, brown adipose tissue (BAT), and skeletal muscle phenotype, hepatic lipid content, insulin resistance via homeostatic assessment model of insulin resistance and AdipoIR, and blood lipids were assessed at death. Remarkably, HCR were protected from OVX-associated increases in adiposity and insulin resistance, observed only in LCR. HCR rats were ∼30% smaller, had ∼70% greater spontaneous physical activity (SPA), consumed ∼10% more relative energy, had greater skeletal muscle proliferator-activated receptor coactivator 1-alpha, and ∼40% more BAT. OVX did not increase energy intake and reduced SPA to the same extent in both HCR and LCR. LCR were particularly affected by an OVX-associated reduction in resting energy expenditure and experienced a reduction in relative BAT; resting energy expenditure correlated positively with BAT across all animals ( r = 0.6; P < 0.001). In conclusion, despite reduced SPA following OVX, high intrinsic aerobic fitness protects against OVX-associated increases in adiposity and insulin resistance. The mechanism may involve preservation of resting energy expenditure.


1977 ◽  
Vol 55 (12) ◽  
pp. 1241-1243 ◽  
Author(s):  
N. Bégin-Heick ◽  
H. M. C. Heick

The activity of lipoprotein lipase (LPL) in the heart, diaphragm, and soleus muscles was markedly increased in cold-acclimated rats and it was even greater in rats treated with oxytetracycline (OTC) while exposed to cold. Other skeletal muscles studied had low and variable activities which were not significantly increased by cold acclimation or by cold plus OTC treatment. It appears therefore that, apart from the heart and the muscles involved in respiratory movements, LPL activity is primarily associated with those muscles which contain a predominance of slow-twitch oxidative fibers, and that the enzyme in muscle, heart, and diaphragm responds to cold acclimation and cold plus OTC treatment in a parallel fashion in these tissues.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 56-56
Author(s):  
Hiroaki Nozawa ◽  
Shigenobu Emoto ◽  
Koji Murono ◽  
Yasutaka Shuno ◽  
Soichiro Ishihara

56 Background: Systemic chemotherapy can cause loss of skeletal muscle mass in colorectal cancer (CRC) patients in the neoadjuvant and palliative settings. However, it is largely unknown how the body composition is changed by chemotherapy rendering unresectable CRC to resectable disease or how it affects the prognosis. This study aimed at elucidating the effects of systemic chemotherapy on skeletal muscles and survival in stage IV CRC patients who underwent conversion therapy. Methods: We reviewed 98 stage IV CRC patients who received systemic chemotherapy in our hospital. According to the treatment setting, patients were divided into the ‘Conversion’, ‘Neoadjuvant chemotherapy (NAC)’, and ‘Palliation’ groups. The cross-sectional area of skeletal muscles at the third lumbar level and changes in the skeletal muscle index (SMI), defined as the area divided by height squared, during chemotherapy were compared among patient groups. The effects of these parameters on prognosis were analyzed in the Conversion group. Results: The mean SMI increased by 8.0% during chemotherapy in the Conversion group (n = 38), whereas it decreased by 6.2% in the NAC group (n = 18) and 3.7% in the Palliation group (n = 42, p < 0.0001). Moreover, patients with increased SMI during chemotherapy had a better overall survival (OS) than those whose SMI decreased in the Conversion group (p = 0.021). The increase in SMI was an independent predictor of favorable OS on multivariate analysis (hazard ratio: 0.26). Conclusions: Stage IV CRC patients who underwent conversion to resection often had an increased SMI. As such an increase in SMI further conveys a survival benefit in conversion therapy, it may be important to make efforts to preserve muscle mass by meticulous approaches, such as nutritional support, muscle exercise programs, and pharmacological intervention even during chemotherapy in patients with metastatic CRC.


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