DOCSLIB.ORG

Snps in FNDC5 (Irisin) Are Associated with Obesity and Modulation of Glucose and Lipid Metabolism in Saudi Subjects Nasser M

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Snps in FNDC5 (Irisin) Are Associated with Obesity and Modulation of Glucose and Lipid Metabolism in Saudi Subjects Nasser M Al-Daghri et al. Lipids in Health and Disease (2016) 15:54 DOI 10.1186/s12944-016-0224-5 RESEARCH Open Access SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects Nasser M. Al-Daghri1,2*, Abdul Khader Mohammed1,2, Omar S. Al-Attas1,2, Osama E. Amer1,2, Mario Clerici3, Amal Alenad4 and Majed S. Alokail1,2 Abstract Background: Irisin is a recently identified myokine that plays an important role in preventing obesity and insulin resistance. We investigated whether the common FNDC5 (irisin precursor) gene variants influence susceptibility to obesity and type 2 diabetes (T2D) and verified the impact of FNDC5 gene variants on serum irisin levels, glucose and lipid metabolism in a Saudi population. Methods: Genomic DNA from 814 (394 T2DM and 414 controls) subjects were genotyped for the five common SNPs (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T) of the FNDC5 gene using the TaqMan genotyping assay. Biochemical parameters and hematic concentrations of irisin and insulin as well as anthropometric indices were collected. Results: Serum irisin levels were higher in T2DM patients compared to controls (p < 0.0001). Analyses of FNDC5 SNPs showed that: 1) The rs3480 GG associates with decreased risk of obesity (p = 0.005; odds ratio: 0.48) and lower body mass index (BMI) values (p = 0.03). In addition, GGAAG was identified as the protective haplotype against risk of obesity (p = 0.001; odds ratio: 0.23). 2) The rs1746661 G allele associates with higher triglyceride (TG) levels (p = 0.019). 3) The rs157069 TT genotype associates with higher fasting insulin (p = 0.029) and HOMA-IR (p = 0.002) as well as with lower circulating irisin levels (p = 0.016). Conclusions: SNPs in FNDC5 gene correlates with obesity and glucose-lipid metabolism possibly because they modulate the serum levels of irisin. Keywords: Obesity, Type 2 diabetes, Irisin, Triglyceride, Insulin, SNPs Background respectively, and the cross-talk between them is critical Obesity and insulin resistance play important roles in for body weight and metabolism [5]. Adipose tissue is the pathogenesis of type 2 diabetes mellitus (T2DM) and composed of two distinct compartments; white adipose are associated with cardiovascular disease [1, 2]. Imbal- tissue (WAT) and brown adipose tissue (BAT). WAT is ance between energy intake and energy expenditure may involved in the regulation of energy homeostasis through cause individuals to be underweight, overweight, or the storage of excess energy, whereas BAT exert a obese [3, 4]. Both skeletal muscle and adipose tissue thermogenic activity, and regulates body temperature by have been shown to function as endocrine organs by se- dissipating energy through heat production [6, 7]. Thus, creting hormones called myokines and adipokines, browning of adipose tissue is hypothesized to improve insulin sensitivity and decrease weight gain [4]. * Correspondence: [email protected] Irisin, a newly described exercise-mediated myokine 1Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry regulates energy metabolism by converting white into Department, College of Science, King Saud University, PO Box, 2455, Riyadh brown fat, may contribute to muscle-adipose tissue 11451, Saudi Arabia 2Biomarkers Research Program, Biochemistry Department, College of Science, cross-talk [5, 8]. Irisin is produced upon cleavage of the King Saud University, Riyadh 11451, Saudi Arabia precursor plasma membrane protein fibronectin type III Full list of author information is available at the end of the article © 2016 Al-Daghri et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Al-Daghri et al. Lipids in Health and Disease (2016) 15:54 Page 2 of 8 domain-containing protein 5 (FNDC5) and enters the cir- All the analyzed SNPs (rs3480, rs1746661, rs1570569 culation [9]. In rodents, overexpression of adenoviral and rs1298190) were in Hardy-Weinberg equilibrium in FNDC5 in high-fat diet fed mice results in increased en- our population (p > 0.05) except rs726344. The role of ergy expenditure, improved obesity (reduced body weight) these common FNDC5 gene variants in predisposition and insulin resistance [10]. Furthermore, irisin is reported to T2DM was analyzed next by multiple logistic regres- to be involved in the pathogenesis of several complications sion model using age, gender, and BMI as covariates. Re- of obesity including dyslipidemia, T2DM, arterial hyper- sults indicated that none of these SNPs were associated tension and metabolic Syndrome [11]. However, there are with T2DM (Table 2). We then analyzed the distribution discrepancies regarding the relation of irisin especially of these SNPs in two BMI-based subgroups, namely, with obesity and T2DM. In some studies, a positive obese or lean. Logistic regression indicated that the association was detected between irisin levels and rs3480 GG genotype is protective against obesity (p = BMI [9, 12, 13], while others reported null [14, 15] or 0.005; OR, 0.48; 95 % CI, 0.28-0.79) (Table 3). This was a negative correlation [11, 12, 16]. From the above men- confirmed by a significant association of the same GG tioned studies, it is evident that either irisin or its precur- genotype of rs3480 with lower BMI values (p = 0.03) sor (FNDC5) has a role to play in pathogenesis of (Table 4). In addition, the distribution frequencies of metabolic diseases, including diabetes and obesity. rs3480 _G + rs1746661_G + rs1298190 _A + rs726344 Until now, only three previous genetic studies have in- _A + rs1570569_G (i.e. GGAAG) haplotype was signifi- vestigated the association of common SNPs in FNDC5 cantly different in obese compared to lean individuals; with obesity [17], insulin sensitivity [18] and glucose me- notably, this haplotype is significantly associated with tabolism [19]. Because of the pivotal role of irisin/ reduced obesity risk (p = 0.001; OR, 0.23; 95 % CI, 0.10– FNDC5 in obesity, insulin resistance and T2DM, we aim 0.53) (Table 5). However, no such differences were to evaluate a possible role of five FNDC5 polymorphisms observed in T2DM group for any of the examined (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/ haplotypes (Table 5). G and rs1570569G/T) in obesity and T2DM phenotypes To determine the effect of FNDC5 SNPs on clinical from Saudi Arabia, a region with a high prevalence of and biochemical parameters, we analyzed the distribu- both conditions [20, 21]. In addition, we examined tion of these variables in relation to the various geno- whether FNDC5 gene variants has any influence on types. After controlling for age, gender, BMI and serum irisin expression and clinical traits related to glu- T2DM, we observed that the rs1746661 G allele was sig- cose and lipid metabolism. nificantly associated with higher triglycerides (TG) levels (p = 0.019) (Table 4). Similarly, the rs3480 AA genotype Results was associated with higher HDL-Cholesterol levels. The anthropometric, clinical and biochemical features of Finally, the rs1570569 TT genotype was significantly asso- individuals enrolled in the study are presented in Table 1. ciated with higher fasting serum insulin (p =0.029) and Table 1 Anthropometric and metabolic characteristics of subjects Group Sub-group Variables T2DM Non-T2DM Obese Lean (N = 394) (N = 420) (N = 293) (N = 264) Male/Female 234/160 188/232 121/172 150/114 Age (years) 53.5 ± 11.2 44.3 ± 12.7** 47.8 ± 11.12 48.4 ± 14.9 BMI (kg/m2) 29.5 ± 6.0 27.2 ± 5.3** 34.9 ± 4.39 21.7 ± 2.8** Systolic BP (mmHg) 128.8 ± 15.1 117 ± 14.0** 125.4 ± 14.2 119 ± 14.3** Diastolic BP (mmHg) 80.6 ± 9.2 77.1 ± 10.1** 79.7 ± 10.2 75.4 ± 7.7** Total Cholesterol (mmol/l) 5.3 ± 1.17 5.0 ± 1.17** 5.18 ± 1.1 5.17 ± 1.2 Triglycerides (mmol/l) 1.7 ± 0.6 1.3 ± 0.56** 1.5 ± 0.57 1.45 ± 0.61* Glucose (mmol/l) 10.1 ± 3.59 5.1 ± 0.93** 10.1 ± 3.59 5.1 ± 0.93* HDL-Cholesterol (mmol/) 0.85 ± 0.34 0.92 ± 0.40* 0.90 ± 0.37 0.87 ± 0.39 LDL-Cholesterol (mmol/) 3.63 ± 1.0 3.56 ± 1.0 3.60 ± 1.0 3.56 ± 1.0 Insulin (μIU/mL) 15.08 ± 9.0 15.9 ± 9.1 17.6 ± 9.4 10.6 ± 6.3** HOMA-IR 6.88 ± 5.5 3.7 ± 2.35** 6.35 ± 4.4 3.0 ± 2.1** Note: “**” denotes p < 0.001, “*” represents p < 0.01. Independent sample t-test was used to compute the difference between studied groups. Data were presented as mean ± standard deviation. Insulin and HOMA-IR are log transformed prior to analysis. Insulin and HOMA-IR values were available for 392 subjects Al-Daghri et al. Lipids in Health and Disease (2016) 15:54 Page 3 of 8 Table 2 Genotype distribution in T2DM vs Non-T2DM subjects Table 3 Genotype distribution in obese vs Non-obese subjects T2DM (%) Non-T2DM (%) Odds ratio (95 CI) P-value Obese (%) Non-obese (%) Odds ratio (95 CI) P-value rs3480 A/G rs3480 A/G GG 78 (20.7) 88 (21.5) 1.29 (0.82–2.03) 0.26 GG 49 (17.2) 66 (25.8) 0.48 (0.28–0.79) 0.005 AG 181 (48.1) 186 (45.4) 1.34 (0.93–1.94) 0.11 AG 136 (47.7) 117 (45.7) 0.76 (0.50–1.15) 0.20 AA 117 (31.1) 136 (32.2) 1.0 1.0 AA 100 (35.1) 73 (28.5) 1.0 1.0 rs1746661 G/T rs1746661 G/T TT 27 (7.2) 25
Load more

Recommended publications
  • Molecular Mechanisms Underlying the Beneficial Effects of Exercise On
    International Journal of Molecular Sciences Review Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders Kévin Nay 1,2, William J. Smiles 1 , Jacqueline Kaiser 1, Luke M. McAloon 1,2, Kim Loh 1,3, Sandra Galic 1, Jonathan S. Oakhill 1,2, Andrew L. Gundlach 3,4 and John W. Scott 1,2,4,* 1 St Vincent’s Institute of Medical Research, Fitzroy, Victoria 3065, Australia; [email protected] (K.N.); [email protected] (W.J.S.); [email protected] (J.K.); [email protected] (L.M.M.); [email protected] (K.L.); [email protected] (S.G.); [email protected] (J.S.O.) 2 Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria 3000, Australia 3 Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia; andrew.gundlach@florey.edu.au 4 The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia * Correspondence: [email protected]; Tel.: +61-3-9288-3632 Abstract: As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used Citation: Nay, K.; Smiles, W.J.; as a sole or combination treatment.
    [Show full text]
  • Current Evidence of the Role of the Myokine Irisin in Cancer
    cancers Review Current Evidence of the Role of the Myokine Irisin in Cancer Evangelia Tsiani 1,2,*, Nicole Tsakiridis 1, Rozalia Kouvelioti 1,3, Alina Jaglanian 1 and Panagiota Klentrou 2,3 1 Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada; [email protected] (N.T.); [email protected] (R.K.); [email protected] (A.J.) 2 Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada; [email protected] 3 Department of Kinesiology, Brock University, St. Catharines, ON L2S 3A1, Canada * Correspondence: [email protected] Simple Summary: Regular exercise/physical activity is beneficial for the health of an individual and lowers the risk of getting different diseases, including cancer. How exactly exercise results in these health benefits is not known. Recent studies suggest that the molecule irisin released by muscles into the blood stream after exercise may be responsible for these effects. This review summarizes all the available in vitro/cell culture, animal and human studies that have investigated the relationship between cancer and irisin with the aim to shed light and understand the possible role of irisin in cancer. The majority of the in vitro studies indicate anticancer properties of irisin, but more animal and human studies are required to better understand the exact role of irisin in cancer. Abstract: Cancer is a disease associated with extreme human suffering, a huge economic cost to health systems, and is the second leading cause of death worldwide. Regular physical activity is associated with many health benefits, including reduced cancer risk. In the past two decades, exercising/contracting skeletal muscles have been found to secrete a wide range of biologically active proteins, named myokines.
    [Show full text]
  • FNDC5 Gene Interactions with Candidate Genes FOXOA3 and AP
    The Author(s) BMC Genomics 2017, 18(Suppl 8):803 DOI 10.1186/s12864-017-4194-4 RESEARCH Open Access Epistasis, physical capacity-related genes and exceptional longevity: FNDC5 gene interactions with candidate genes FOXOA3 and APOE Noriyuki Fuku1*†, Roberto Díaz-Peña2,3†, Yasumichi Arai4, Yukiko Abe4, Hirofumi Zempo1, Hisashi Naito1, Haruka Murakami5, Motohiko Miyachi5, Carlos Spuch6, José A. Serra-Rexach8, Enzo Emanuele7, Nobuyoshi Hirose1 and Alejandro Lucia9 From 34th FIMS World Sports Medicine Congress Ljubljana, Slovenia. 29th September – 2nd October 2016 Abstract Background: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of ‘modifier genes’,maycontributeto explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population. A total of 1565 individuals were studied, subdivided into 822 middle-aged controls and 743 centenarians. Results: We found a FOXOA3 rs2802292 T-allele-dependent association of fibronectin type III domain-containing 5 (FDNC5) rs16835198 with EL: the frequency of carriers of the FOXOA3 rs2802292 T-allele among individuals with the rs16835198 GG genotype was significantly higher in cases than in controls (P < 0.05). On the other hand, among non- carriers of the APOE ‘risk’ ε4-allele, the frequency of the FDNC5 rs16835198 G-allele was higher in cases than in controls (48.4% vs.
    [Show full text]
  • NIH Public Access Author Manuscript Nature
    NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2012 December 14. Published in final edited form as: Nature. ; 481(7382): 463–468. doi:10.1038/nature10777. A PGC1α-dependent myokine that drives browning of white fat and thermogenesis $watermark-text $watermark-text $watermark-text Pontus Boström1, Jun Wu1, Mark P. Jedrychowski2, Anisha Korde1, Li Ye1, James C. Lo1, Kyle A. Rasbach1, Elisabeth Almer Boström3, Jang Hyun Choi1, Jonathan Z. Long1, Shingo Kajimura4, Maria Cristina Zingaretti5, Birgitte F. Vind6, Hua Tu7, Saverio Cinti5, Kurt Højlund6, Steven P. Gygi2, and Bruce M. Spiegelman1,* 1Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, floor 11, Boston, MA, 02115, USA 2Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA 3Renal Division, Brigham and Women’s Hospital, Harvard Medical School 4UCSF Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco 5Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Electron Microscopy Unit-Azienda Ospedali Riuniti, Ancona 60020, Italy 6Diabetes Research Center, Department of Endocrinology, Odense University Hospital, Denmark 7LakePharma, Inc. 530 Harbor Blvd, Belmont CA 94002 Abstract Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional coactivator PGC1α Here we show that PGC1α expression in muscle stimulates an increase in expression of Fndc5, a membrane protein that is cleaved and secreted as a new hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown fat-like development.
    [Show full text]
  • The Acute Effects of Swimming Exercise on PGC-1-FNDC5/Irisin
    H OH metabolites OH Article The Acute Effects of Swimming Exercise on PGC-1α-FNDC5/Irisin-UCP1 Expression in Male C57BL/6J Mice Eunhee Cho 1, Da Yeon Jeong 2, Jae Geun Kim 2,3 and Sewon Lee 4,5,6,* 1 Department of Human Movement Science, Graduate School, Incheon National University, Incheon 22012, Korea; [email protected] 2 Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea; [email protected] (D.Y.J.); [email protected] (J.G.K.) 3 Institute for New Drug Development, Division of Life Sciences, Incheon National University, Incheon 22012, Korea 4 Division of Sport Science, College of Arts & Physical Education, Incheon National University, Incheon 22012, Korea 5 Sport Science Institute, College of Arts & Physical Education, Incheon National University, Incheon 22012, Korea 6 Health Promotion Center, College of Arts & Physical Education, Incheon National University, Incheon 22012, Korea * Correspondence: [email protected]; Tel.:+82-32-835-8572 Abstract: Irisin is a myokine primarily secreted by skeletal muscles and is known as an exercise- induced hormone. The purpose of this study was to determine whether the PGC-1α -FNDC5 /Irisin- UCP1 expression which is an irisin-related signaling pathway, is activated by an acute swimming exercise. Fourteen to sixteen weeks old male C57BL/6J mice (n = 20) were divided into control (CON, n n = 10) and swimming exercise groups (SEG, = 10). The SEG mice performed 90 min of acute swimming exercise, while control (non-exercised) mice were exposed to shallow water (2 cm of depth) for 90 min.
    [Show full text]
  • Irisin – a Myth Rather Than An
    OPEN Irisin – a myth rather than an SUBJECT AREAS: exercise-inducible myokine TRANSCRIPTION Elke Albrecht1*, Frode Norheim2*, Bernd Thiede3, Torgeir Holen2, Tomoo Ohashi4, Lisa Schering1, FAT METABOLISM Sindre Lee2, Julia Brenmoehl5, Selina Thomas6, Christian A. Drevon2, Harold P. Erickson4 & Steffen Maak1 Received 1Institute for Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology, D-18196 Dummerstorf, Germany, 2Department 8 December 2014 of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway, 3The Biotechnology Centre of Oslo, University of Oslo, 0317 Oslo, Norway, 4Department of Cell Biology, Duke University, Durham, NC 27710, USA, 5Institute of Accepted Genome Biology, Leibniz Institute for Farm Animal Biology, D-18196 Dummerstorf, Germany, 6Swiss Institute of Equine Medicine 9 February 2015 (ISME), Vetsuisse Faculty, University of Berne, 1580 Avenches, Switzerland. Published 9 March 2015 The myokine irisin is supposed to be cleaved from a transmembrane precursor, FNDC5 (fibronectin type III domain containing 5), and to mediate beneficial effects of exercise on human metabolism. However, evidence for irisin circulating in blood is largely based on commercial ELISA kits which are based on Correspondence and polyclonal antibodies (pAbs) not previously tested for cross-reacting serum proteins. We have analyzed four commercial pAbs by Western blotting, which revealed prominent cross-reactivity with non-specific requests for materials proteins in human and animal sera. Using recombinant glycosylated and non-glycosylated irisin as positive should be addressed to controls, we found no immune-reactive bands of the expected size in any biological samples. A FNDC5 S.M. (maak@fbn- signature was identified at ,20 kDa by mass spectrometry in human serum but was not detected by the dummerstorf.de) commercial pAbs tested.
    [Show full text]
  • Irisin As a Multifunctional Protein: Implications for Health and Certain Diseases
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Jagiellonian Univeristy Repository medicina Review Irisin as a Multifunctional Protein: Implications for Health and Certain Diseases Paulina Korta 1 , Ewa Poche´c 1,* and Agnieszka Mazur-Biały 2 1 Department of Glycoconjugate Biochemistry, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland 2 Department of Ergonomics and Exercise Physiology, Faculty of Health Sciences, Jagiellonian University, Medical College, Grzegorzecka 20, 31-531 Krakow, Poland * Correspondence: [email protected]; Tel.: +48-12-664-64-67 Received: 29 June 2019; Accepted: 12 August 2019; Published: 15 August 2019 Abstract: Sedentary life style is considered to be an independent risk factor for many disorders, including development of type 2 diabetes, obesity, immune dysfunction, asthma, and neurological or coronary heart disease. Irisin is released from myocytes during physical activity, and acts as a link between muscles and other tissues and organs. This myokine is produced as a result of proteolytic cleavage of FNDC5 protein present in the membrane of myocytes. Secretion of irisin is regulated by N-linked oligosaccharides attached to the protein molecule. The two N-glycan molecules, which constitute a significant part of the irisin glycoprotein, regulate the browning of adipocytes, which is the most important function of irisin. A receptor specific for irisin has still not been discovered. In some tissues irisin probably acts via integrins, which are widely expressed transmembrane receptors. Many studies have confirmed the multifunctional role of irisin and the beneficial effects of this molecule on body homeostasis.
    [Show full text]
  • View a Copy of This Licence, Visit
    Zhang et al. Journal of Ovarian Research (2021) 14:107 https://doi.org/10.1186/s13048-021-00851-8 RESEARCH Open Access Long-term intermittent cold exposure affects peri-ovarian adipose tissue and ovarian microenvironment in rats Li Zhang†, Gaihong An†, Shuai Wu, Jing Wang, Danfeng Yang, Yongqiang Zhang* and Xi Li* Introduction contents gradually increase as follicles develop. These Cold is a significant environmental stress factor. Studies steroids, non-steroid hormones, and growth factors act have shown that exposure to cold environments can as regulatory factors and constitute the microenviron- cause local or whole-body temperatures to decrease, ment that determines follicle growth and development. posing a severe threat to overall health [1–3]. Cold The ovarian microenvironment plays a vital role in ovar- exposure has adverse effects on the female reproductive ian function and follicle development. However, the ef- system [4–6], affecting ovarian [7] and uterine [4] func- fects of cold exposure on ovarian function and the tions and hormone secretion [8]. Possible reasons in- ovarian microenvironment have not been well- clude: imbalance of ET-1 and its receptor expression elucidated. leads to local tissue microvascular circulatory distur- Studies have shown that the development and matur- bances [9]; affects follicular development by activating ation of follicles prior to ovulation are primarily regu- sympathetic nerve activity in the ovary [10, 11]; Cold lated by the central neuroendocrine system and growth stress can also cause reproductive hormone disorders, factors and hormones found in the local ovarian micro- causing uterine arteries to contract, resulting in reduced environment [13, 14]. Peri-ovarian adipose tissue blood flow [12].
    [Show full text]
  • The Role of Irisin in Cancer Disease
    cells Review The Role of Irisin in Cancer Disease Agnieszka Pinkowska 1 , Marzenna Podhorska-Okołów 2, Piotr Dzi˛egiel 3,4 and Katarzyna Nowi ´nska 3,* 1 Department of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland; [email protected] 2 Department of Ultrastructure Research, Wroclaw Medical University, 50-368 Wroclaw, Poland; [email protected] 3 Department of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland; [email protected] 4 Department of Physiotherapy, University School of Physical Education, 51-612 Wroclaw, Poland * Correspondence: [email protected]; Tel.: +48-71-784-1354; Fax: +48-71-784-0082 Abstract: Irisin (Ir) is an adipomyokine that is involved in the regulation of metabolic processes. It also influences processes related to inflammation, including cancer. Initially, Ir was considered a hormone secreted by skeletal muscles in response to physical exercise. Further studies showed that Ir is also present in other healthy tissues, organs, and plasma. It influences the change in phenotype of white adipose tissue (WAT) into brown adipose tissue (BAT). It increases mitochondrial biogenesis and affects the expression of thermogenin (UCP1). This adipomyokine has also been found in many tumor tissues and in the serum of cancer patients. Studies are underway to determine the association between Ir and carcinogenesis. It has been confirmed that Ir inhibits in vitro proliferation, migration, and invasion. It is involved in the inhibition of epithelial–mesenchymal transition (EMT). Additionally, Ir affects the expression of the transcription factor Snail, which is involved in EMT, and inhibits transcription of the gene encoding E-cadherin, which is characteristic of epithelial-derived cells.
    [Show full text]
  • Theranostics NAD+-Boosting Therapy Alleviates Nonalcoholic Fatty Liver
    Theranostics 2021, Vol. 11, Issue 9 4381 Ivyspring International Publisher Theranostics 2021; 11(9): 4381-4402. doi: 10.7150/thno.53652 Research Paper NAD+-boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin Dong-Jie Li1,2,3*, Si-Jia Sun2,3*, Jiang-Tao Fu1*, Shen-Xi Ouyang2,3*, Qin-Jie Zhao,4 Li Su,5 Qing-Xi Ji,2,3 Di-Ynag Sun1, Jia-Hui Zhu2,3, Guo-Yan Zhang2,3, Jia-Wei Ma2,3, Xiu-Ting Lan,2,3 Yi Zhao,2,3 Jie Tong2,3, Guo-Qiang Li,1,6 Fu-Ming Shen2,3, Pei Wang1,2,3 1. Department of Pharmacology, School of Pharmacy, Second Military Medical University/Naval Medical University, Shanghai, China. 2. Department of Pharmacy, School of Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. 3. Tongji University School of Medicine, Shanghai, China. 4. Department of Organic Chemistry, School of Pharmacy, Second Military Medical University/Naval Medical University, Shanghai, China. 5. Institute of Translational Medicine, Shanghai University, Shanghai, China. 6. School of Life Science, East China Normal University, Shanghai, China. *These authors contributed equally to this work. Corresponding author: Prof. Pei Wang, Ph.D, MD, Department of Pharmacology, School of Pharmacy, Second Military Medical University/Naval Medical University, Shanghai, China. Tel: 86-21-81871276; E-mail: [email protected]. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
    [Show full text]
  • Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences
    Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences The atalogue for ransmission enetics in rabs C T G A CTGA Database CDKN2B Antisense RNA Alternative Names including vascular endothelial cells and smooth CDKN2BAS coronary muscle cells. Antisense Noncoding RNA in the INK4 Locus ANRIL Epidemiology in the Arab World Record Category Saudi Arabia Gene locus Abdulazeez et al., (2016) performed a case-control study in order to investigate the association of 12 WHO-ICD risk variants located at 9p21.3 with myocardial N.B.:Classification not applicable to gene loci. infarction (MI) in Saudi Arabian population. The study included 250 Saudi patients with CAD who Incidence per 100,000 Live Births had experienced an MI and 252 age matched N/A to gene loci healthy controls with no history of CAD. Results showed a significant difference in the genotypic OMIM Number distribution of four SNPs (rs564398, rs4977574, 613149 rs2891168, and rs1333042) in the CDKN2B-AS1 gene between cases and controls. The study Mode of Inheritance identified three protective haplotypes (TAAG, N/A AGTA and GGGCC) and a risk haplotype (TGGA) for the development of CAD. This study was in Gene Map Locus line with previous studies conducted worldwide 9p21.3 indicating that the SNPs located in the intronic region of the CDKN2B-AS1 gene were associated Description with CAD. The CDKN2BAS gene is located near the CDKN2A-CDKN2B gene and codes for an References antisense non-coding RNA. Although the exact AbdulAzeez S, Al-Nafie AN, Al-Shehri A, Borgio function of this gene and the ncRNA it codes for is JF, Baranova EV, Al-Madan MS, Al-Ali RA, Al- unknown, there is evidence pointing to the fact that Muhanna F, Al-Ali A, Al-Mansori M, Ibrahim MF, it may regulate the expression of nearby protein Asselbergs FW, Keating B, Koeleman BP, Al-Ali coding genes, including CDKN2A, CDKN2B, and AK.
    [Show full text]
  • Assessment of Pep, Fndc5, C2c12, Pgc1α Pattern of Genes Expression
    ndrom Sy es tic & e G n Asadi et al., J Genet Syndr Gene Ther 2016, 7:6 e e n G e f T o Journal of Genetic Syndromes & DOI: 10.4172/2157-7412.1000314 h l e a r n a r p u y o J ISSN: 2157-7412 Gene Therapy Research Article Open Access Assessment of Pep, Fndc5, C2c12, Pgc1α Pattern of Genes Expression during Differentiation of Human Embryonic Stem Cells into Heart Cells Shahin Asadi1*, Zahra Gholizadeh1, Mahsa Sadat Mir Jamali2 and Mina Niknia2 1Research Center for Stem Cell and Drug Applied Research Center, Tabriz University of Medical Sciences in modern biology, Iran 2Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran Abstract FNDC5 gene with another protein called Xuemei Proxy (PEP) is a 209 amino acid protein coding. These genes mainly in heart tissue, skeletal muscle and brain expressed. This study aimed to clarify the pattern of expression of this gene in mouse embryonic cells Heart cells taken. The mouse embryonic stem cells as a model for cardiac differentiation induced by ascorbic acid used and the pattern of expression of PEP at certain stages of differentiation were analyzed by Real-Time PCR technique. The results show a dramatic increase in PEP gene expression in the adult cardiomyocytes. PEP increased expression of genes may have a role in later stages cardiogenesis is possible that further studies are needed to identify it. Keywords: Protein proxy xuemei; Cardiac differentiation; Embryonic The ectodomain was proposed to be cleaved to give a soluble stem cells and mice; Real-time PCR peptide hormone named irisin.
    [Show full text]