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      Serum Irisin Level Can Predict the Severity of Coronary Artery Disease in Patients with Stable Angina

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          Abstract

          Background and Objectives

          The recently discovered myokine irisin has a proposed role in adipose tissue metabolism. The aim of this study was to evaluate the relationship between serum irisin level and the coronary artery severity in patients with stable coronary artery disease (CAD).

          Subjects and Methods

          Sixty-three patients who underwent coronary angiography (CA) diagnosed with stable CAD and twenty-six patients with normal coronary artery (NCA) were enrolled in the study. Stable CAD patients were divided into two groups as high synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score (≥23) and lower SYNTAX score (<23). Serum irisin level measurement was carried out using human irisin colorimetric enzyme-linked immunosorbent assay (ELISA) commercial kit (AG-45A-0046EK-KI01, Adipogen, San Diego, CA, USA) as recommended by the manufacturer's protocol.

          Results

          The patients with stable CAD with a higher SYNTAX score (score ≥23) had significantly lower serum irisin levels (127.91±55.38 ng/mL), as compared the patients with a low SYNTAX score (score <23) (224.69±92.99 ng/mL) and control group (299.54±123.20 ng/mL). Irisin levels showed significant differences between all groups (p<0.001).

          Conclusion

          Serum irisin level is an independent predictor of coronary artery severity in patients with stable CAD.

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          Muscles, exercise and obesity: skeletal muscle as a secretory organ.

          Bente K. Pedersen, Mark A. Febbraio (2012)
          During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.
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            Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance.

            José Moreno-Navarrete, Francisco Ortega, Marta Serrano … (2013)
            Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes. Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed. In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels. Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.
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              Lower circulating irisin is associated with type 2 diabetes mellitus.

              Jian-Jun Liu, Melvin D S Wong, Wan Ching Toy … (2013)
              Irisin is a novel myokine secreted in response to PPAR-γ co-activator-1α (PGC-1α) activation. Earlier studies suggested that PGC-1α expression and activity were lower in myocytes in type 2 diabetes mellitus (T2DM). Therefore, we hypothesize that circulating irisin levels are lower in T2DM patients. In this observational study, we recruited 96 T2DM subjects and 60 non-diabetic control subjects. Among T2DM subjects, 38% were on insulin treatment, 78% were taking statins and 72% were taking renin-angiotensin system antagonists. Circulating irisin was quantified by ELISA and its association with markers of metabolic phenotype was analyzed by Pearson bivariate correlation and multiple linear regression. Circulating irisin was significantly lower in individuals with T2DM compared with non-diabetic controls (T2DM 204 ± 72 ng/ml vs. non-diabetic control 257 ± 24 ng/ml, p < 0.0001). In non-diabetic subjects, circulating irisin was correlated with age (r = 0.398, p < 0.01), BMI (r = 0.387, p < 0.01), total cholesterol (r = 0.341, p < 0.01), total triglycerides (r = 0.299, p < 0.05), fasting blood glucose (r = 0.430, p < 0.01) and diastolic blood pressure (r = 0.306, p < 0.05). Multiple linear regression model revealed that BMI (β = 0.407, p = 0.012) and FBG (β = 0.315, p = 0.034) were associated with irisin in non-diabetic subjects after adjusting for multiple co-variates. However, similar analysis in T2DM subjects didn't reveal significant association between circulating irisin and major markers of metabolic phenotype. Circulating irisin is lower in T2DM compared with non-diabetic controls. Plasma irisin levels appear to be associated with important metabolic factors in non-diabetic subjects but not in individuals with type 2 diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Korean Circ J
                Journal ID (iso-abbrev): Korean Circ J
                Journal ID (publisher-id): KCJ
                Title: Korean Circulation Journal
                Publisher: The Korean Society of Cardiology
                ISSN (Print): 1738-5520
                ISSN (Electronic): 1738-5555
                Publication date (Print): January 2017
                Publication date (Electronic): 23 December 2016
                Volume: 47
                Issue: 1
                Pages: 44-49
                Affiliations
                [1 ]Dışkapı Yıldırım Beyazıt Training and Research Hospital, Cardiology Clinic, Ankara, Turkey.
                [2 ]Türkiye Yüksek Ihtisas Training and Research Hospital, Cardiology Clinic, Ankara, Turkey.
                Author notes
                Correspondence: Çağrı Yayla, MD, Türkiye Yüksek İhtisas Training and Research Hospital, Sıhhiye, Ankara 06500, Turkey. Tel: 90-533-6449643, Fax: 90-312-3061000, cagriyayla@ 123456gmail.com
                Article
                DOI: 10.4070/kcj.2016.0079
                PMC ID: 5287186
                PubMed ID: 28154590
                SO-VID: a9e1f227-3a0b-420e-bcbe-b01938f047e3
                Copyright © Copyright © 2017 The Korean Society of Cardiology
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 28 February 2016
                Date revision received : 01 July 2016
                Date accepted : 07 July 2016
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: coronary artery disease,atherosclerosis,irisin
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: coronary artery disease, atherosclerosis, irisin

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