Turkiye Klinikleri Journal of Medical Sciences

.: REVIEW
Zayıflama Miyokini: FNDC5/İrisin ile İlgili Güncel Yaklaşımlar Üzerine Bir Derleme: Geleneksel Derleme
A Traditional Review of the Slimming Myokine: Current Approaches to FNDC5/Irisin
Diler US ALTAYa
aOrdu Üniversitesi Sağlık Bilimleri Fakültesi, Beslenme ve Diyetetik Bölümü, Ordu, Türkiye
Turkiye Klinikleri J Med Sci. 2022;42(2):138-43
doi: 10.5336/medsci.2022-89253
Article Language: TR
Full Text
ÖZET
İskelet kası, kalp ve beyinde eksprese edilen transmembran proteini olarak bilinen FNDC5 (fibronektin Tip 3 domainini içeren 5. protein), 2002 yılında keşfedildi ve yaklaşık 10 yıl boyunca bu membran proteini görmezden gelindi. 2012 yılında, özellikle akut ve yoğun egzersize cevap olarak iskelet kası FNDC5'inin ektodomain kısmı (N-terminal domaini), bilinmeyen bir proteaz tarafından kesilerek dolaşıma aktarıldı ve irisin olarak adlandırıldı. İrisinin beyaz yağ dokusuna, üzerinde bulunan integrin reseptörüne bağlanarak, peroksizom proliferatör aktive edici reseptör alfa aracılıklı UCP1 ekspresyonu ve mitokondri sayısını artırdığı, beyaz yağ dokusunun kahverengi yağ dokusuna dönüşmesini uyardığı yapılan deneysel çalışmalarla gösterildi. Normalde beyaz yağ dokusu soğuğa maruz kalındığında, beyin ve kalp gibi vital organları korumaya almak için bu değişimi gerçekleştirmektedir. Ancak beklenmedik bir şekilde, egzersize yanıt olarak beyaz yağ dokusunun değişiminin gerçekleştiği ve enerjinin adenozin trifosfat olarak değil, ısı olarak açığa çıktığı gösterilmiştir. Buna dayanarak, irisin molekülünün zayıflama, insülin sensitivitesi ve glukoz homeostazına aracılık edebileceği önerilmektedir. 2012-2022 yılları arasında, irisin miyokininin rolünü keşfetmek üzere 1.000'den fazla makale yayımlanmıştır ve özellikle yağ dokusu ve metabolizmadaki etkilerini aydınlatmak amacıyla çalışmalar devam etmektedir. Ancak çelişkili sonuçlar mevcuttur ve bu durumun, bazı çalışmalarda insan ve hayvan serum ve plazma numunelerinde irisin seviyesinin doğru ölçülmemesinden kaynaklandığı gösterilmiştir. Bu derlemede, irisin ile ilgili ölçüm yöntemleri, birçok hastalığın tedavisi açısından ümit verici olabileceği düşünülen rekombinant irisin enjeksiyonu ve FNDC5 geni nakavt edilmiş fare çalışmalarıyla ilgili güncel yaklaşımlara yer verilecektir.

Anahtar Kelimeler: FNDC5/irisin; ölçüm yöntemleri; rekombinant irisin
ABSTRACT
FNDC5 (fibronectin Type 3 domain containing protein 5), known as the transmembrane protein expressed in skeletal muscle, heart and brain, was discovered in 2002 and this membrane protein was ignored for about 10 years. In 2012, in response to particularly acute and intense exercise, the ectodomain portion (N-terminal domain) of skeletal muscle FNDC5 was cleaved by an unknown protease, and this portion was circulated and named irisin. Experimental studies have shown that irisin binds to the integrin receptor on white adipose tissue, increasing peroxisome proliferator-activated receptor alpha-mediated UCP1 expression and mitochondria count, and stimulating transformation of white adipose tissue into brown adipose tissue. Normally, when the white adipose tissue is exposed to cold, it performs this change to protect vital organs such as the brain and heart. However, unexpectedly, it has been shown that white adipose tissue changes in response to exercise and that energy is released as heat, not adenosine triphosphate. Based on this, it is suggested that the irisin molecule may mediate attenuation, insulin sensitivity, and glucose homeostasis. Between 2012-2022, more than 1,000 articles were published to explore the role of irisin myokine, and studies are continuing to elucidate its effects on adipose tissue and metabolism. However, there are conflicting results and it has been shown in some studies that the irisin level in human and animal serum and plasma samples is not measured correctly. In this review, current approaches about measurement methods related to irisin, recombinant irisin injection, which is thought to be promising for the treatment of many diseases, and FNDC5 gene knockout mouse studies will be discussed.

Keywords: FNDC5/irisin; measurement methods; recombinant irisin
REFERENCES:
  1. Liu C, Lin JD. PGC-1 coactivators in the control of energy metabolism. Acta Biochim Biophys Sin (Shanghai). 2011;43(4):248-57. [Crossref]  [PubMed]  [PMC] 
  2. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-8. [Crossref]  [PubMed]  [PMC] 
  3. Us Altay D, Keha EE, Ozer Yaman S, Ince I, Alver A, Erdogan B, et al. Investigation of the expression of irisin and some cachectic factors in mice with experimentally induced gastric cancer. QJM. 2016;109(12): 785-90. [Crossref]  [PubMed] 
  4. Teufel A, Malik N, Mukhopadhyay M, Westphal H. Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes. Gene. 2002;297(1-2):79-83. [Crossref]  [PubMed] 
  5. Erickson HP. Irisin and FNDC5 in retrospect: an exercise hormone or a transmembrane receptor? Adipocyte. 2013;2(4):289-93. [Crossref]  [PubMed]  [PMC] 
  6. Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, et al. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism. 2012;61(12):1725-38. [Crossref]  [PubMed]  [PMC] 
  7. Castillo-Quan JI. From white to brown fat through the PGC-1α-dependent myokine irisin: implications for diabetes and obesity. Dis Model Mech. 2012;5(3):293-5. [Crossref]  [PubMed]  [PMC] 
  8. Takada Y, Ye X, Simon S. The integrins. Genome Biol. 2007;8(5):215. [Crossref]  [PubMed]  [PMC] 
  9. Czyz M. Regulacja ekspresji integryn. Acta Haematol Pol. 2000;31:17-23.
  10. Vamvini MT, Aronis KN, Panagiotou G, Huh JY, Chamberland JP, Brinkoetter MT, et al. Irisin mRNA and circulating levels in relation to other myokines in healthy and morbidly obese humans. Eur J Endocrinol. 2013;169(6):829-34. [Crossref]  [PubMed]  [PMC] 
  11. Maak S, Norheim F, Drevon CA, Erickson HP. Progress and challenges in the biology of FNDC5 and irisin. Endocr Rev. 2021;42(4):436-56. [Crossref]  [PubMed]  [PMC] 
  12. Kim H, Wrann CD, Jedrychowski M, Vidoni S, Kitase Y, Nagano K, et al. Irisin mediates effects on bone and fat via αV integrin receptors. Cell. 2018;175(7):1756-68.e17. Erratum in: Cell. 2019;178(2):507-8. [Crossref]  [PubMed]  [PMC] 
  13. Polyzos SA, Mathew H, Mantzoros CS. Irisin: a true, circulating hormone. Metabolism. 2015;64(12):1611-8. [Crossref]  [PubMed] 
  14. Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM, et al. Detection and Quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 2015;22(4):734-40. [Crossref]  [PubMed]  [PMC] 
  15. Aslım HP, Bulut O. Western blot. J Adv VetBio Sci Tech. 2021;6(1):45-56. [Crossref] 
  16. Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013;18(5):649-59. [Crossref]  [PubMed]  [PMC] 
  17. Löffler D, Müller U, Scheuermann K, Friebe D, Gesing J, Bielitz J, et al. Serum irisin levels are regulated by acute strenuous exercise. J Clin Endocrinol Metab. 2015;100(4):1289-99. [Crossref]  [PubMed] 
  18. Brenmoehl J, Albrecht E, Komolka K, Schering L, Langhammer M, Hoeflich A, et al. Irisin is elevated in skeletal muscle and serum of mice immediately after acute exercise. Int J Biol Sci. 2014;10(3):338-49. [Crossref]  [PubMed]  [PMC] 
  19. Boster Bio [Internet]. © 1993-2021 Boster Biological Technology. ELISA Kits, Antibodies, Antibody Company. Available from: [Link] 
  20. Perakakis N, Triantafyllou GA, Fernández-Real JM, Huh JY, Park KH, Seufert J, et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol. 2017;13(6):324-37. [Crossref]  [PubMed]  [PMC] 
  21. Aslan R, Alp HH, Eryılmaz R, Huyut Z, Sevim M, Araz Ş, et al. Can the irisin be a biomarker for prostate cancer? A case control study. Asian Pac J Cancer Prev. 2020;21(2):505-9. [Crossref]  [PubMed]  [PMC] 
  22. Tang L, Tong Y, Zhang F, Chen G, Zhang YC, Jobin J, et al. The association of circulating irisin with metabolic risk factors in Chinese adults: a cross-sectional community-based study. BMC Endocr Disord. 2019;19(1):147. [Crossref]  [PubMed]  [PMC] 
  23. Xiong Y, Wu Z, Zhang B, Wang C, Mao F, Liu X, et al. Fndc5 loss-of-function attenuates exercise-induced browning of white adipose tissue in mice. FASEB J. 2019;33(5):5876-86. [Crossref]  [PubMed] 
  24. Luo Y, Qiao X, Ma Y, Deng H, Xu CC, Xu L. Disordered metabolism in mice lacking irisin. Sci Rep. 2020;10(1):17368. Erratum in: Sci Rep. 2021;11(1):22021. [Crossref]  [PubMed]  [PMC] 
  25. Reza MM, Subramaniyam N, Sim CM, Ge X, Sathiakumar D, McFarlane C, et al. Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy. Nat Commun. 2017;8(1):1104. [Crossref]  [PubMed]  [PMC] 
  26. Reza MM, Sim CM, Subramaniyam N, Ge X, Sharma M, Kambadur R, et al. Irisin treatment improves healing of dystrophic skeletal muscle.Oncotarget. 2017;8(58):98553-66. [Crossref]  [PubMed]  [PMC] 

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