Myokine Research Articles

MiRNA and Myokines in Patients With PAH

miRNA and Myokines in Patients With PAH

The Effect of Korean Dance & Yoga Multi-exercise on Myokine in Post Menopause Obesity Women

The Effect of Korean Dance & Yoga Multi-exercise on Myokine in Post Menopause Obesity Women

A Review on the Role of Irisin in Insulin Resistance and Type 2 Diabetes Mellitus.

Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane- spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin’s function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the ‘browning’ of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic β cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.

Myokine Signaling Blockade Prevents Androgen Deprivation Therapy Induced Sarcopenia and Suppresses Tumor Growth

The mainstay treatment of recurrent or metastatic prostate cancers is androgen deprivation therapy (ADT). These advanced cancers progress relatively slowly, and patients often receive ADT for years, meaning that any side effects of ADT can have a significant impact on the health of the prostate cancer patients. One of The mainstay treatment of recurrent or metastatic prostate cancers is androgen deprivation therapy (ADT). These advanced cancers progress relatively slowly, and patients often receive ADT for years, meaning that any side effects of ADT can have a significant impact on the health of the prostate cancer patients. One of the most frequent side effects, possibly afflicting as many as 200,000 patients, is progressive loss of muscle mass (sarcopenia), typically accompanied by functional deficits in these patients. Exercise therapy has shown promise as a potential treatment for ADT‐induced sarcopenia, but has not been found to reverse the functional deficits, indicating it is urgent to improve this therapy or develop additional or complementary therapies. We have previously investigated ADT‐induced sarcopenia in a non‐tumor bearing mouse model. The castration‐induced changes closely resembled the loss of skeletal muscle strength and body composition that occurs in ADT treated patients. ActRIIB‐Fc (Acceleron's investigational ‘tool’ drug RAP‐031), which binds and blocks multiple myokines, inhibited sarcopenia in our normal mouse model. We examined the expression of TGFß family members that bind RAP‐031 in our model and found that muscle levels of myostatin (by immunoblot), activins A, AB, B and GDF11 (all by ELISA performed on muscle extracts) all increase over time, but with distinctive kinetics. Here we used castrated PBCre4 × PTENf/f tumor‐bearing mice and measured tumor volume (by ultrasound and 3D‐image reconstruction), body composition (by NMR), muscle mass, fat mass (by micro‐CT), grip strength and expression of TGFß family members. ADT of PTEN‐deficient tumor‐bearing mice reduces muscle mass, overall lean body mass (LBM), increases fat and reduces grip strength, similar to non‐tumor bearing mice. RAP‐031 treatment of castrated PTEN‐deficient mice reversed these phenotypic changes that resemble ADT side effects in human patients. Surprisingly, myokine inhibition also induces prostate tumor regression in the absence of ADT, and increased the rate and degree of castration induced prostate tumor regression in this model. These results suggests that myokines might be both biomarkers and potential targets for therapy to reduce this co‐morbidity in prostate cancer patients and may also control tumor growth directly.Support or Funding InformationThis work was supported by a New York State Prostate Cancer Research Program Award C030321 and grant HHS‐6‐15SF from the S.A.S. Foundation (K.L.N), and National Cancer Institute grant CA151753 (J.J.K.) and P30AR061307 and P30CA016056. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Myokines and osteokines in muscle-bone interactions

Sarcopenia and osteoporosis are two common diseases with adverse effects on the health of the elderly and share many characteristics.As target organs of the two diseases, muscles and bones are closely connected, not only in anatomy and physiology, but also in pathophysiological processes.Initially, mechanical stimulation was conducted to explain the relationship between muscle and bone at the macroscopic level.Currently, research is increasingly focused at the cellular and molecular levels.Both muscle and bone tissues can secrete a number of growth factors, cytokines, polypeptides, and so on.Myokines include fibroblast growth factor-2(FGF-2), myostatin, irisin, insulin-like growth factor-1(IGF-1), interleukins, musclin, among others.Osteokines comprise osteocalcin, fibroblast growth factor-23, IGF-1, vascular endothelial growth factor, etc.In this review, we summarize the roles of myokines and osteokines in muscle-bone interactions. Key words: Muscular diseases; Osteoporosis

Omega-3 Fatty Acid Could Increase One of Myokines in Male Patients with Coronary Artery Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

Omega-3 fatty acids have a protective role against cardiovascular disease and these protective properties are attributed to its anti-inflammatory effects. Myokines have anti-inflammatory properties and thereby reduce low-grade inflammation. Irisin, as a myokine, is considered to be therapeutic for human metabolic diseases. This study was conducted to determine the effects of Omega-3 fatty acids supplementation on serum irisin in men with coronary artery disease (CAD). This study was an 8-week randomized, double-blind, placebo-controlled trial. Forty-eight CAD male patients (Omega-3, n = 24; control, n = 24) were randomly assigned to either Omega-3 or control groups by permuted block randomization method. Only the participants with more than 50% stenosis in at least one major coronary vessel were included. A total of 3 participants in the control group were excluded from the study. Forty-five participants (Omega-3, n = 24; control, n = 21) completed the study. Participants took Omega-3 fatty acids supplement (720 mg eicosapentaenoic acid plus 480 mg docosahexaenoic acid) or placebo (edible paraffin) for 8 weeks. Serum irisin, high-sensitivity C-reactive protein (hs-CRP), lipid profile and anthropometric indices, body composition, and food intake were assessed before and after intervention. Statistical analyses were performed using SPSS software. Paired t-test was used for evaluating within-group effects from baseline. Variables with normal distribution were compared by independent t-test between 2 groups. Compared to placebo, Omega-3 fatty acids increased serum irisin (P = 0.044) and decreased serum hs-CRP (P = 0.018) and LDL cholesterol (P = 0.031). Omega-3 fatty acids supplementation did not result in any significant changes in anthropometric measurements, blood pressure, serum lipids except for serum LDL, fasting blood glucose, body composition or serum insulin levels (all P > 0.05). Omega-3 fatty acids supplementation could elevate serum irisin in male patients with CAD. Also, these fatty acids may able to decrease serum hs-CRP and LDL cholesterol.

Treatment with r-irisin prevents and recovers disuse-induced bone loss and muscle atrophy

Irisin is a hormone-like myokine secreted from skeletal muscle in response to exercise. We previously showed that treatment with recombinant Irisin (r-Irisin) in healthy mice improved cortical bone mass and geometry, supporting the idea that Irisin recapitulates some of the most important benefits of physical exercise on the skeleton and plays protective role on bone health (1). Here we show that treatment with r-Irisin prevented bone loss in hind-limb suspended mice when administered during suspension and induced recovery of bone mass when mice were injected after bone loss due to a suspension period of 4 weeks. MicroCT analysis of femurs showed that r-Irisin preserved both cortical and trabecular bone mineral density, and prevented the dramatic decrease of the trabecular bone volume fraction. Moreover, r-Irisin inhibited muscle mass decline during unloading, keeping proper fiber cross-sectional area. Notably, the decrease in myosin type II expression (MyHC II) in vastus lateralis of unloaded mice treated with r-Irisin was completely prevented. Our data reveal that r-Irisin treatment protects from disuse induced bone loss and muscle atrophy in mice. If these results will translate to humans, they may support a promising clinical strategy for the prevention and treatment of both osteoporosis and sarcopenia, particularly applicable to those patients who cannot perform physical activity, as occurs during aging, immobility and microgravity during space flight missions.

Effects of recombinant Irisin on the musculoskeletal system of hind-limb suspended mice

We previously showed that Irisin, a myokine released from skeletal muscle after physical exercise, plays a central role in the control of bone mass, driving positive effects on cortical mineral density and geometry in vivo (1). Here we demonstrated that r-Irisin treatment prevents bone loss in hind-limb suspended mice when administered during suspension and recovers bone mass when mice were injected after a suspension period (4 weeks) during which they developed bone loss. Micro computed tomography of femurs showed that r-Irisin treatment positively affected both cortical and trabecular bone. As expected, unloaded mice treated with vehicle displayed a remarkable decrease of cortical and trabecular bone mineral density (BMD), whereas in Irisin-treated unloaded mice no loss of BMD was observed with respect to control mice kept under normal loading. Likewise, by treating mice after they already developed disuse-induced bone loss, r-Irisin was able to restore the damaged mineral component. Furthermore, trabecular bone volume fraction (BV/TV), which dramatically decreased in unloaded mice, was prevented by r-Irisin therapy. In particular, r-Irisin treatment preserved the number of trabeculae (Tb.N) and the fractal dimension, an index of optimal micro-architectural complexity of trabecular bone.We also showed that r-Irisin treatment protects muscle mass suffering from atrophy during unloading. Thus, unloaded mice treated with vehicle displayed a severe loss of muscle mass, as confirmed by ~ 60% decline of vastus lateralis weight and ~33% decrease of fiber cross-sectional area. Conversely, Irisin-treated unloaded mice showed no loss of muscle weight and similar fiber cross-sectional area to control mice. Our data reveal for the first time that r-Irisin treatment prevents and retrieves disuse-induced bone loss and muscle atrophy. These findings may lead to develop an Irisin-based therapy for the prevention and treatment of osteoporosis and sarcopenia in all patients who cannot perform physical activity, as occurs during aging and immobility, and it could also represent a countermeasure for astronauts exposed to microgravity during space flight missions.This work was supported in part by ERISTO grant (to M.G.), by MIUR grant ex60% (to M.G.) and by SIOMMMS grant (to G.C.).

Analysis of Musculoskeletal Systems and Their Diseases. Integrated treatments for osteoporosis toward harmony of bone and muscle

Osteoporosis and sarcopenia directly affect healthy life expectancy in elderly people ; therefore, both diseases become social problem around the world. Sarcopenia increases the risk of osteoporotic fracture. Thus, not only agents affecting bone tissue directly but also treatments for sarcopenia are important for management of osteoporosis. Recently, it has been shown that there is an interaction between bone and muscle. Several hormones affect muscle and bone simultaneously. Moreover, myokines secreted from muscle are reported to regulate bone metabolism. On the other hand, several systemic and local factors derived from bone also affect muscle tissue. Therefore, further studies are necessary to develop the integrated treatments for osteoporosis toward harmony of bone and muscle.

Irisin injected mice display increased tibial cortical mineral density and polar moment of inertia

It has been recently reported that, after physical activity, the skeletal muscle releases Irisin, the newly identified myokine able of driving transition of white adipocytes into brown [1]. This result supported the role of skeletal muscle as endocrine organ, suggesting that it could target other tissues besides adipose tissue. In our previous work, we demonstrated that conditioned media collected from primary myoblasts of exercised mice were able to increase OB differentiation and this effect was Irisinmediated [2]. Here we show that Irisin has positive effect on cortical mineral density and geometry in vivo. Young male mice were injected with r-Irisin and cortical bone adaptation was analyzed by micro-CT at tibial midshaft. Our results show that cortical tissue mineral density is significantly increased in Irisin-injected mice compared to vehicle-injected littermates (+7.15%; p<0.01). Furthermore, this higher density of calcium hydroxyapatite at cortical site is accompanied by increase in periosteal circumference (+7.5%; p<0.03) and polar moment of Inertia (pMOI +19,21%; p<0,01). A greater pMOI indicates stronger resistance of a long bone to torsion and, together with higher bone mineral density, suggests higher protection against fracture. The effect of Irisin is fully comparable to the effect of physical activity that is widely accepted method for increasing bone mineral density and bone size in healthy populations. In view of further proving the involvement of Irisin in bone metabolism, we validate its direct effect on osteoblasts in vitro. Phosphorylation of the MAP kinase ERK and the expression of Atf4 were significantly increased after Irisin treatment, as well as ALP and pro-Collagen I mRNA expression. Our data highlight a novel link in muscle-fat-bone axis demonstrating that Irisin targets bone tissue directly, driving positive effects on cortical mineral density and geometry in vivo. These findings would expand the research of exercise-mimetic drugs that might be widely used to treat osteoporotic patients who are suffering from immobilization and cannot perform physical activity.

Get that myokine burn

Get that myokine burn

Irisin, the novel myokine responsible for benefits of physical exercise on bone

It has been recently reported that, after physical exercise activity, the skeletal muscle releases Irisin, the newly identified myokine able of driving transition of white adipocytes into brown, following a phenomenon known as the browning response. This result suggested that skeletal muscle is crucial in the regulation of energy homeostasis, supporting its role as endocrine organ that targets adipose tissue by promoting energy expenditure. In accordance with this new finding, we demonstrated that conditioned media (CM) collected from primary myoblasts of exercised mice were able to induce osteoblast differentiation in a greater extent than those of mice housed in resting conditions and this effect is Irisin-mediated. In view of further proving the involvement of Irisin in bone metabolism, we validate its direct effect on osteoblasts by using r-Irisin. Here we show that phosphorylation of MAP kinase ERK and expression of Atf 4 (p<0,001), the key trascription factor of osteoblast differentiation, were significantly increased after Irisin treatment. Furthermore, ALP and pro-Collagen I mRNA resulted up regulated (p<0,001), as we already demonstrated by treating osteoblasts with conditioned medium from primary myoblasts of exercised mice. To recapitulate in vivo the effect of physical exercise, we injected mice with r-Irisin. Our results show that BV/TV of Irisin-treated mice was higher than vehicle-injected mice. In elderly, the severe decline of skeletal muscle function, known as Sarcopenia, is associated with impaired function of bone (Osteopenia) and these two simultaneous losses of function lead to increased risk of bone fractures. In order to reveal new strategies for treatment of sarcopenia and osteopenia, we also analyzed the effect of physical activity in old mice. Our findings demonstrate that mRNA levels of the most relevant bone proteins resulted up regulated in ex-vivo osteoblast obtained from exercised old mice compared with mice kept in resting conditions. Our data highlight a novel link in muscle-fat-bone axis demonstrating that Irisin targets bone tissue directly. Future perspectives, based on these studies, could satisfy the ongoing research of exercise-mimetic therapies with anabolic action on the skeleton.

Myokines: Do they really exist?

Myokines: Do they really exist?