Irisin, a recently discovered myokine, has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in patients with heart failure (HF), both with preserved (HFpEF) or reduced (HFrEF) ejection fraction. We have therefore evaluated the circulating irisin levels in HFpEF and HFrEF patients, correlating them with metabolic parameters and total antioxidant capacity (TAC), as index of oxidative stress.
We selected 933 cases and 869 controls sequenced in this study. Variant (c.3034−1GA) in the protocadherin 11 X-linked protein – PCDH11X. P50 HD055751 (EHC), RO1 MH057881 (BD), and R01 MH061009 (JSS). Ronemus M, Yamrom B, Lee YH, Leotta A, Kendall J, Marks S, Lakshmi B, Pai D, Ye K, et al.
Irisin was significantly higher in HFpEF than in HFrEF patients (7.72 ± 0.76 vs 2.77 ± 0.77 ng/ml, respectively). An inverse correlation between irisin and TAC was found in HFpEF, but not in HFrEF. Conversely, no correlation was present with HOMA index.
These data support the hypothesis that a different pathophysiological mechanism is involved in the two HF subtypes, and oxidative stress modulates irisin secretion. Defective brain hormonal signaling has been associated with Alzheimer's disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released on cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also expressed in the hippocampus.
Here we show that FNDC5/irisin levels are reduced in AD hippocampi and cerebrospinal fluid, and in experimental AD models. Knockdown of brain FNDC5/irisin impairs long-term potentiation and novel object recognition memory in mice. Conversely, boosting brain levels of FNDC5/irisin rescues synaptic plasticity and memory in AD mouse models.
Peripheral overexpression of FNDC5/irisin rescues memory impairment, whereas blockade of either peripheral or brain FNDC5/irisin attenuates the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. By showing that FNDC5/irisin is an important mediator of the beneficial effects of exercise in AD models, our findings place FNDC5/irisin as a novel agent capable of opposing synapse failure and memory impairment in AD. Half a decade ago, transmembrane protein fibronectin type III domain-containing protein 5 (FNDC5) was found to be cleaved as a novel myokine irisin, which burst into prominence for browning of white adipose tissue during exercise. However, FNDC5, the precursor of irisin, has been paid relatively little attention compared with irisin despite evidence that FNDC5 is associated with the metabolic syndrome, which accounts for one-fourth of the world's adult population and contributes to diabetes, cardiovascular disease and all-cause mortality. Besides N-terminal and C-terminal sequences, the FNDC5 protein contains an irisin domain and a short transmembrane region. FNDC5 has shown to be widely distribute in different tissues and is highly expressed in heart, brain, liver, and skeletal muscle.
Clinical studies have demonstrated that FNDC5 is essential for maintaining metabolic homeostasis and dysregulation of FNDC5 will lead to systemic metabolism imbalance and the onset of metabolic disorders. Growing evidence has suggested that FNDC5 gene polymorphisms are related to health and disease in different human populations. Additionally, FNDC5 has been found relevant to the regulation of metabolism and metabolic syndrome through diverse upstream and downstream signaling pathways in experimental studies. The present review summarizes the characteristics, clinical significance, and molecular mechanisms of FNDC5 in metabolic syndrome and proposes a novel concept that FNDC5 is activated by forming a putative ligand-receptor complex. Knowledge about the role of FNDC5 may be translated into drug development and clinical applications for the treatment of metabolic disorders. Irisin is secreted by muscle, increases with exercise, and mediates certain favorable effects of physical activity.
In particular, irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear, and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins, and biophysical studies identify interacting surfaces between irisin and αV/β5 integrin.
Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5 (or irisin) completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling. Identification of the irisin receptor should greatly facilitate our understanding of irisin's function in exercise and human health. Results: Only in women did asprosin (P = 0.001) (15', 30', 60', and 24 h after exercise) and irisin (P. Epicardial fat located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk.
Irisin is a myokine produced by skeletal muscle after physical exercise, and originally described as a molecule able to promote the browning of white adipose tissue and energy expenditure. In order to decrease cardiovascular risk, it has been proposed as a promising therapeutic target in obesity and type 2 diabetes. We investigated the relationships between serum concentrations of irisin and the adipokines adiponectin and leptin and body fat including epicardial fat in patients undergoing cardiovascular surgery.
We obtained serum samples from 93 patients undergoing cardiovascular surgery (age 69.6 (SD 12.8) years, BMI 24.1 ± 4.8 kg/m2). Computed tomography (CT) and echocardiographic data were obtained from the routine preoperative examination. Subcutaneous fat area (SFA, cm2) and visceral fat area (VFA, cm2) near the umbilicus were automatically measured using the standard fat attenuation range. Epicardial fat area (EFA, cm2) was measured at the position where the heart became a long axis image with respect to the apex of the heart in the coronal section image. Total body fat mass, body fat percentage, and skeletal muscle volume (SMV) were estimated using bioelectrical impedance analysis (BIA). Serum irisin concentration was measured by enzyme-linked immunosorbent assay, and compared with adiponectin and leptin concentrations.
The data were also compared with the clinical biochemical data. EFA was strongly correlated with BMI (P = 0.0001), non-HDL-C (P = 0.029), TG (P = 0.004), body fat mass (P = 0.0001), and body fat percentage (P = 0.0001). Serum leptin concentration showed a significant positive correlation with BMI (P = 0.0001) and TG (P = 0.001). Adiponectin, but not irisin, showed a significant negative correlation with BMI (P = 0.006) and TG (P = 0.001).
Serum leptin level had a significant positive correlation with EFA, VFA, and SFA. In contrast, the serum adiponectin level was significantly negatively correlated with EFA, VFA, and SFA. The serum irisin level was also negatively correlated with EFA (r = -0.249, P = 0.015), and SFA (r = -0.223, P = 0.039), and tended to correlate with VFA (r = -0.198, P = 0.067).
The serum level of adiponectin was negatively correlated with that of leptin (r = -0.296, P = 0.012), but there were no significant correlations between irisin and either adiponectin or leptin. Multivariate linear regression demonstrated that EFA showed a positive association with serum leptin level (β = 0.438, P = 0.0001) and a negative correlation with serum irisin level (β = -0.204, P = 0.038) and serum adiponectin level (β = -0.260, P = 0.015) after adjusting for age, sex, and BMI. The present study provided the first evidence of associations of the serum irisin and adipokines (adiponectin and leptin) concentrations with epicardial fat in cardiovascular surgery patients.
Irisin may play a role in preventing excess adiposity including epicardial fat, and consequently cardiovascular risk in patients.This publication used the irisin EIA kit (EK-067-29) from Phoenix Pharmaceuticals for irisin serum level assay. Irisin, an adipomyokine identified in 2012, has been investigated in association with common pregnancy complications, including gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. The objective of this study is to examine the potential role of irisin in preterm birth (PTB) by comparing its level between mothers with term and preterm labor.
Maternal peripheral blood and cord blood samples were collected from 30 mothers who delivered prematurely and from 35 mothers who delivered at term. Irisin concentrations were measured in all samples using ELISA, and four common single nucleotide polymorphisms in the irisin gene were determined (rs16835198, rs726344, rs3480, and rs1746661). Univariable and multivariable regression modeling was applied to evaluate maternal and cord blood irisinconcentrations in relation to preterm/term labor. Irisin concentration in umbilical cord blood was found to be associated with PTB in the univariable model (p = 0.046). On the other hand, no differences in maternal blood irisin levels between mothers with preterm and term deliveries were established.
To the best of our knowledge, this is the first study determining irisin levels in term and preterm deliveries in maternal peripheral blood and umbilical cord blood. Our study shows a possible association between cord blood irisin concentration and PTB occurrence.This publication used the irisin EIA kit (EK-067-29) from Phoenix Pharmaceuticals for irisin plasma level assay. METHODS: Fifteen HD patients (5 men, 44.4 ± 15.1 years old) were studied and served as their own controls. High intensity (single session) intradialytic strength exercises consisted of three sets of ten repetitions with four different movements in both lower limbs during 30 minutes. Blood samples were collected on different days (exercise and non-exercise day) at exactly the same time (30 and 60 minutes after the start of dialysis session). Plasma irisin levels were measured by ELISA assay and anthropometric and biochemical parameters were evaluated. RESULTS: Irisin plasma levels were significantly reduced in both exercise day (125.0 ± 18.5 to 117.4 ± 15.0 ng/mL, p=0.02) and non-exercise day (121.5 ± 13.7 to 115.4 ± 17.2 ng/mL, p=0.02) after 60 minutes of dialysis.
CONCLUSION: These data suggest that intense intradialytic strength exercise was unable to increase the circulating concentration of irisin in HD patients. Moreover, our data show that after one hour of dialysis session, irisin plasma levels may be reduced.This publication used the irisin EIA kit (EK-067-29) from Phoenix Pharmaceuticals for irisin serum level assay. RESULTS: Exposure of C2C12 myocytes to ATRA led to increased fatty acid consumption and decreased cellular triacylglycerol levels without affecting glucose uptake, and induced the expression of the myokine irisin at the mRNA and secreted protein level in a dose-response manner.
ATRA stimulatory effects on FAO-related genes and the Fndc5 gene (encoding irisin) were reproduced by agonists of peroxisome proliferator-activated receptor β/δ and retinoid X receptors, but not of retinoic acid receptors, and were partially blocked by an AMP-dependent protein kinase inhibitor. Circulating irisin levels were increased by 5-fold in ATRA-treated mice, linked to increased Fndc5 transcription in liver and adipose tissues, rather than skeletal muscle. Immunohistochemistry analysis of FNDC5 suggested that ATRA treatment enhances the release of FNDC5/irisin from skeletal muscle and the liver and its accumulation in interscapular brown and inguinal white adipose depots. CONCLUSION: These results provide new mechanistic insights on how ATRA globally stimulates FAO and enhances irisin secretion, thereby contributing to leaning effects and improved metabolic status.This publication used the irisin EIA kit (EK-067-29) from Phoenix Pharmaceuticals for circulating irisin level measurement. BACKGROUND/AIMS: Vascular calcification, which involves an active cellular transformation of vascular smooth muscle cells into bone forming cells, is prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear.
We presume that irisin, a newly identified myokine also may play roles in vascular calcification in hemodialysis patients. This study aims to evaluate serum irisin levelsand establish their relation to vascular calcification and other parameters in hemodialysis patients. RESULTS: Serum irisin concentrations were significantly lower in hemodialysis patients than in controls 52.8 (22.0, 100.0) vs. 460.8 (434.8, 483.4) ng/ml, P.
The mechanisms underlying the metabolic improvements following aerobic exercise training remain poorly understood. The primary aim of this study was to determine if an adipomyokine, irisin, responded to acute exercise was associated with the metabolic adaptations to chronic aerobic exercise in obese youth. The acute response to exercise was assessed in 11 obese youth following 45-min acute bouts of aerobic (AE) and resistance exercise (RE). The irisin area under the curve (pre-exercise, 15, 30, and 45 min) during these AE sessions were the main exposure variables.
The primary outcome measure was the change in insulin sensitivity using the Matsuda index, following 6 weeks of RE training, delivered for 45 min, three times per week at 60-65% 1RM. Participants were also categorized as either responders (above) or nonresponders (below) based on the percentage change in the Matsuda index following the 6-week intervention. Irisin increased significantly during the acute bout of AE from 29.23 ± 6.96 to 39.30 ± 7.05 ng/mL; P = 0.028, but not significantly during the RE session (P = 0.182).
Absolute and relative change in irisin during the acute bout of AE was associated with absolute and relative change in Matsuda index (r = 0.68; P = 0.022 and r = 0.63; P = 0.037) following the 6-week RE intervention. No such association was observed with the irisin responseto acute RE (all P 0.05). Responders to the 6-week RE intervention displayed a fourfold greater irisin response to acute AE (90.0 ± 28.0% vs. 22.8 ± 18.7%; P = 0.024) compared to nonresponders. Irisin increases significantly following an acute bout of AE, but not RE, and this response is associated with a greater improvement in insulin sensitivity in response to chronic resistance training.This publication used the irisin EIA kit (EK-067-29) from Phoenix Pharmaceuticals for quantification of human irisin plasma level.
Irisin is a myokine encoded in its precursor fibronectin type III domain containing 5 (FNDC5). It is abundantly expressed in cardiac and skeletal muscle, and is secreted upon the activation of peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1 alpha). We aimed to study the role of irisin on cardiac function and muscle protein regulation in zebrafish.
Western blot analyses detected the presence of irisin protein (23 kDa) in zebrafish heart and skeletal muscle, and irisin immunoreactivity was detected in both tissues. Irisin siRNA treated samples did not show bands corresponding to irisin in zebrafish. In vitro studies found that treatment with irisin (0.1 nM) downregulated the expression of PGC-1 alpha, myostatin a, and b, while upregulating troponin C mRNA expression in zebrafish heart and skeletal muscle. Exogenous irisin (0.1 and 1 ng/g B.W) increased diastolic volume, heart rate and cardiac output, while knockdown of irisin (10 ng/g B.W) showed opposing effects on cardiovascular function. Irisin (1 and 10 ng/g B.W) downregulated PGC-1 alpha, myostatin a and b, and upregulated troponin C and troponin T2D mRNA expression. Meanwhile, knockdown of irisin showed opposing effects on troponin C, troponin T2D and myostatin a and b mRNAs in zebrafish heart and skeletal muscle.
Collectively, these results identified muscle proteins as novel targets of irisin, and added irisin to the list of peptide modulators of cardiovascular physiology in zebrafish.This publication used the irisin antibody (H-067-17) and c-terminal peptide (067-17) from Phoenix Pharmaceuticals for in vivo and in vitro assays. Type 2 diabetes mellitus (T2DM) is caused by insulin resistance and β cell dysfunction. In recent studies reported that several markers associated with insulin sensitivity in skeletal muscle, Adiponectin and other parameters, such as fatty acid-binding protein (FABP4), have been reported to regulate insulin resistance, but it remains unclear which factor mostly affects insulin resistance in T2DM. In this cross-sectional study, we evaluated the relationships between several kinds of biomarkers and insulin resistance, and insulin secretion in T2DM and healthy controls. We recruited 30 participants (12 T2DM and 18 non-diabetic healthy controls). Participants underwent a meal tolerance test during which plasma glucose, insulin and serum C-peptide immunoreactivity were measured. We performed a hyperinsulinemic-euglycemic clamp and measured the glucose-disposal rate (GDR).
The fasting serum levels of adiponectin, insulin-like growth factor-1, irisin, autotaxin, FABP4 and interleukin-6 were measured by ELISA. We found a strong negative correlation between FABP4 concentration and GDR in T2DM (r = -0.657, p = 0.020).
FABP4 also was positively correlated with insulin secretion during the meal tolerance test in T2DM (IRI (120): r = 0.604, p = 0.038) and was positively related to the insulinogenic index in non-DM subjects (r = 0.536, p = 0.022). Autotaxin was also related to GDR. However, there was no relationship with insulin secretion. We found that serum FABP4 concentration were associated with insulin resistance and secretion in T2DM. This suggests that FABP4 may play an important role in glucose homeostasis.This publication used the irisin EIA kit (EK-067-29) from Phoenix Pharmaceuticals.
RESULTS: Serum irisin levels were lower in nondiabetic peritoneal dialysis patients (17.02ng/ml) compared with healthy controls (22.17ng/ml, P. Exercise provides many health benefits, including improved metabolism, cardiovascular health, and cognition. We have shown previously that FNDC5, a type I transmembrane protein, and its circulating form, irisin, convey some of these benefits in mice. However, recent reports questioned the existence of circulating human irisin both because human FNDC5 has a non-canonical ATA translation start and because of claims that many human irisin antibodies used in commercial ELISA kits lack required specificity. In this paper we have identified and quantitated human irisin in plasma using mass spectrometry with control peptides enriched with heavy stable isotopes as internal standards. This precise state-of-the-art method shows that human irisin is mainly translated from its non-canonical start codon and circulates at ∼ 3.6 ng/ml in sedentary individuals; this level is increased to ∼ 4.3 ng/ml in individuals undergoing aerobic interval training. These data unequivocally demonstrate that human irisin exists, circulates, and is regulated by exercise.
As a link between exercise and metabolism, irisin is assumed to be involved in increased total body energy expenditure, reduced body weight, and increased insulin sensitivity. Although our recent evidence supported the contribution of irisin to vascular endothelial cell (ECs) proliferation and apoptosis, further research of irisin involvement in the angiogenesis of ECs was not conclusive. In the current study, it was found that irisinpromoted Human Umbilical Vein Endothelial Cell (HUVEC) angiogenesis via increasing migration and tube formation, and attenuated chemically-induced intersegmental vessel (ISV) angiogenic impairment in transgenic TG (fli1: GFP) zebrafish. It was further demonstrated that expression of matrix metalloproteinase (MMP) 2 and 9 were also up-regulated in endothelial cells. We also found that irisin activated extracellular signal-related kinase (ERK) signaling pathways. Inhibition of ERK signaling by using U0126 decreased the pro-migration and pro-angiogenic effect of irisin on HUVEC.
Also, U0126 inhibited the elevated expression of MMP-2 and MMP-9 when they were treated with irisin. In summary, these findings provided direct evidence that irisin may play a pivotal role in maintaining endothelium homeostasis by promoting endothelial cell angiogenesis via the ERK signaling pathway. Objective: Betatrophin has recently been introduced as a novel adipokine/hepatokine, which promotes pancreatic β cell proliferation and improves glucose tolerance in several mouse models of insulin resistance.
However, regulation of betatrophin in gestational diabetes mellitus (GDM), as well as its association with markers of obesity, such as glucose and lipid metabolism, inflammation, and renal function, have not been elucidated.Design and methods: Circulating betatrophin was quantified in 74 women with GDM and 74 healthy and gestational age-matched controls by ELISA. In a subset of the study population comprising of 85 patients (41 previous controls, 44 previous women with GDM), postpartum betatrophin levels were measured in a follow-up study.Results: Median (interquartile range) serum betatrophin levels were higher in women with GDM (1.79 (0.53)?g/l) as compared to non-diabetic pregnant controls (1.58 (0.44)?g/l) (P=0.002). In multivariate analysis, GDM status was an independent and positive predictor of circulating betatrophin (P=0.001). Furthermore, betatrophin levels were significantly higher during gestation (1.70 (0.53)?g/l) as compared to postpartum levels (1.55 (0.66)?g/l) (P=0.028). Moreover, postpartum irisin remained a positive and independent predictor of postpartum betatrophin concentrations.Conclusions: Women with GDM have significantly higher betatrophin levels as compared to healthy pregnant controls and GDM status positively predicts circulating betatrophin.
Furthermore, postpartum levels are significantly lower as compared to betatrophin concentrations during pregnancy. Moreover, irisin is a significant predictor of postpartum betatrophin levels.This publication used an Irisin kit from Phoenix Pharmaceuticals.
Irisin is a newly identified myokine. Several studies have reported irisin concentrations in patients with gestational diabetes mellitus (GDM), but because of smaller sample sizes, the data from previous reports showed a wide range in serum/plasma irisin. Therefore, the present investigation is designed to summarize a precise confidence interval of circulating irisin in participants with GDM from a cross-sectional study in Chinese population and a meta-analysis for validation.
Serum irisin was tested in patients with GDM and healthy controls (newly diagnosed cases: 61 and matched controls: 61) in the cross-sectional study. The two groups of participants were matched with for age and pregnancy duration. Furthermore, we did a comprehensive meta-analysis to confirm whether serum/plasma irisin differs between participants with GDM and controls. Articles reported “circulating irisin and GDM” in Medline, PubMed, and EMBase were obtained, with the key word “myokine” or “irisin”. The comparison was analyzed by Review Manager 5.2. In the cross-sectional investigation, serum irisin showed a significant lower level in the GDM patients, compared with that in the control group.
In the meta-analysis study, the summarized results of the present 5 studies in which 632 participants were included indicated that there was a lower level irisin of -58.68 ng/ml 95% confidence interval (CI)(-113.42, -3.93, P=0.04) in GDM patients than in the control group. The present cross-sectional investigation and meta-analysis is the first to show significant lower circulating irisin in subjects with GDM.This publication used an Irisin kit from Phoenix Pharmaceuticals. Vascular complications are the major causes of death in patients with diabetes, and endothelial dysfunction is the earliest event in vascular complications of diabetes. It has been reported that plasma irisin level is significantly reduced in patients with type 2 diabetic patients.
The present study aimed to investigate whether irisin improved endothelial function in type 2 diabetes as well as the underlying mechanisms. The type 2 diabetes model was established by feeding C57BL/6 mice with high-fat diet. The type 2 diabetic mice exhibited reduced serum irisin level and impaired endothelial function. Irisin treatment (0.5mg/kg/d) for two weeks improved vascular function based on the evaluation of endothelium-dependent vasorelaxation and p-VASP levels. To investigate the direct endothelial protective effects of irisin, diabetic aortic segments were incubated with irisin(1?g/ml) ex vivo. Exposure to irisin improved endothelium-dependent vasorelaxation of diabetic aortas.
Mechanically, the diabetic aortic segments exhibited increased oxidative/nitrative stresses. Irisin reduced the diabetes-induced oxidative/nitrative stresses evidenced by reducing overproduction of superoxide and peroxynitrite, and down-regulation of iNOS and gp91phox. To further investigate the protective effects of irisin on endothelial cells and the underlying mechanisms, human umbilical vein endothelial cells (HUVECs) cultured in high-glucose/high-fat (HG/HF) medium were pre-incubated with irisin. Irisin (1?g/ml) reduced the oxidative/nitrative stresses and apoptosis induced by HG/HF in HUVECs probably via inhibiting activation of PKC-?/NADPH oxidase and NF-?B/iNOS pathways. Taken together, irisin alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses through inhibiting signaling pathways implicating PKC-?/NADPH oxidase and NF-?B/iNOS, suggesting that irisin may be a promising molecule for the treatment of vascular complications of diabetes. Irisin is a newly identified hormone induced in muscle and adipose tissues by physical activity.
This protein and its encoding gene have been identified in the brain; in addition, the precursor for irisin, FNDC5, can cross the blood-brain barrier. The fact that irisin is secreted during exercise together with the lower resting heart rate in athletes prompted us to investigate the effect of irisin on cardiac-projecting vagal neurons of nucleus ambiguus, a key regulatory site of heart rate. In vitro experiments in cultured nucleus ambiguus neurons indicate that irisin activates these neurons, inducing an increase in cytosolic Ca(2+) concentration and neuronal depolarization. In vivo microinjection of irisin into the nucleus ambiguuspromotes bradycardia in conscious rats. Our study is the first to report the effects of irisin on the neurons controlling the cardiac vagal tone and to link a myokine to a cardioprotective role, by modulating central cardiovascular regulation.This publication used an Irisin recombinant protein from Phoenix Pharmaceuticals.
INTRODUCTION: Irisin is a newly identified 112 amino acid hormone, derived as a product of fibronectin type III domain containing 5 (FNDC5), which is highly related to metabolic activity in skeletal muscle and brown fat. The effects of irisin on cardiovascular functions are unknown.PURPOSE: To explore the effects of central and peripheral irisin on cardiovascular functions.METHODS: Irisin was either administrated into 3rd ventricle of rats or intravenously, and its effects on blood pressure and cardiac contractibility measured.RESULTS: Administration of recombinant human irisin into the 3rd brain ventricle of rats activated neurons in the paraventricular nuclei of the hypothalamus. Central administration of irisin increased blood pressure and cardiac contractibility.
Exogenous irisin reversed atenolol-induced inhibition of cardiac contractibility. In contrast, peripheral administration of irisin reduced blood pressure in both control and spontaneously hypertensive rats. Irisin dilated mesenteric artery rings through ATP-sensitive potassium channels.CONCLUSION: Our studies indicate that central and peripheral irisin may differentially regulate cardiovascular activities.This publication used an Irisin recombinant protein from Phoenix Pharmaceuticals. Irisin is a novel myokine produced by skeletal muscle. However, its metabolic role is poorly understood.
In the present study, irisin induced glucose uptake in differentiated skeletal muscle cells. It increased AMP-activated protein kinase (AMPK) phosphorylation and the inhibition of AMPK blocked glucose uptake. It also increased reactive oxygen species (ROS) generation.
N-acetyl-cysteine (NAC), a ROS scavenger, blocked irisin-induced AMPK phosphorylation. Moreover, irisin activated p38 mitogen-activated protein kinase (MAPK) in an AMPK-dependent manner. The inhibition and knockdown of p38 MAPK blocked irisin-induced glucose uptake. A colorimetric absorbance assay showed that irisin stimulated the translocation of GLUT4 to the plasma membrane, and that this effect was suppressed in cells pre-treated with a p38 MAPK inhibitor or p38 MAPK siRNA. In primary cultured myoblast cells, irisin increased the concentration of intracellular calcium. STO-609, a calcium/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor, blocked irisin-induced AMPK phosphorylation, implying that calcium is involved in irisin-mediated signaling.
Our results suggest that irisin plays an important role in glucose metabolism via the ROS-mediated AMPK pathway in skeletal muscle cells.This publication used an Irisin recombinant protein from Phoenix Pharmaceuticals. To elucidate the effects of endurance training on circulating irisin levels in young and middle-aged/older adults, and to determine the association between endurance training-induced alteration of irisin and reduction in body fat.
Twenty-five healthy young (age 21 ± 1 years; 16 men, 9 women) and 28 healthy middle-aged/older adults (age 67 ± 8 years; 12 men, 16 women) participated in the study. Each age cohort was divided into two groups: the endurance-training group (14 young, 14 middle-aged/older) and the control group.
Subjects in the training groups completed an 8-week endurance-training program (cycling at 60-70% peak oxygen uptake Formula: see textO2peak for 45 min, 3 days/week). Before and after the intervention, we evaluated serum irisin level, Formula: see textO2peak, and body composition. The increase in Formula: see textO2peak in the young and middle-aged/older training groups after the intervention period was significantly greater than those in the young and middle-aged/older control groups (P. Irisin is a newly discovered factor that is secreted by skeletal muscle and plays an important role in the homeostasis and metabolism of energy balance. This study used irisin radiolabeled with 125I and small-animal SPECT/CT imaging to investigate the metabolic elimination and distribution ofirisin in vivo. Irisin was labeled with 125I using the Iodogen method.
Small-animal SPECT/CT imaging was performed on C57/B16 mice at 15, 30, 60, 120, and 240?min after receiving a tail vein injection, and the radioactive distribution in the organs of mice was determined at 15, 60, and 120?min. Small-animal SPECT/CT imaging revealed the highest level of radioactivity in the gallbladder followed by the liver and kidney.
Ehc 933 011 Ken Bell Attorney
Radioactivity decreased gradually with time in all organs. The radioactive distribution in the mice organs also showed that the highest%ID/g was in the gallbladder followed by the kidney and liver, and decreased gradually with time. The radioactivity in the gastric system reached its highest level at 60?min. Finally, our study showed the metabolic clearance of 125I-irisin is achieved primarily through the hepatobiliary and renal system and provided the basis for the clinical application of irisin. Context: Polycystic ovary syndrome (PCOS) is an insulin resistance (IR) state, like obesity and type 2 diabetes mellitus (T2DM). BACKGROUND: although there is evidence of correlation between irisin and osteoporotic fractures, previous studies have not elucidated the relationship between irisin and either lean or fat mass.
The main aim of this study is to investigate the relationship between irisin and body composition in postmenopausal women with osteoporosis and the impact of irisin levels on fragility vertebral fractures.METHODS: In this cross-sectional study, 36 overweight subjects affected by at least one vertebral osteoporotic fracture confirmed by a X-ray vertebral morphometry and 36 overweight non-osteoporotic subjects were enrolled. Serum irisin levels were measured using an irisin competitive ELISA.
We evaluated lumbar spine and hip BMD and body composition using dual energy X-ray absorptiometry. To measure and monitor daily physical activity, each subject wore an armband for approximately 72 hours.RESULTS: No significant correlations were found between irisin and BMD at any site and between irisin with either lean or fat mass. Serum levels ofirisin were not correlated with the daily physical activity. Serum irisin levels were lower in subjects with previous osteoporotic fractures than in controls (p= 0.032) and the difference in irisin levels remained significant after adjustment for creatinine (p=0.037), vitamin D (p=0.046), lean mass (p=0.02), lumbar BMD (p=0.023) and femoral BMD (p=0.032).CONCLUSION: our data confirm an inverse correlation between irisin levels and vertebral fragility fractures but no significant correlation was found with BMD or lean mass. Irisin may play a protective role on bone health independent of BMD but further studies are needed to clarify the relationship between irisin and bone metabolism. This article is protected by copyright.
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