Yeni Hormonlar: R-Spondin-1, Nesfatin-1 ve İrisin

Abstract

Wnt modülatörlerinden R-spondin ailesi, çeşitli hastalık süreçlerinde görevli olan β-katenin/Wnt sinyal aktivitesini artırma yeteneğinden oldukça dikkat çekmektedir. Metabolik bozukluklar, obezite ve diyabet gibi hastalıklarla ilişkilendirilen irisin ise bu hastalıkların tedavisinde ve izlenmesinde umut vaat edici olarak görülen bir diğer hormondur. Öte yandan anoreksijenik bir hormon olan nesfatin-1’in, obezite ve diyabetin yanı sıra psikiyatrik bozukluklar ve nörojenik hastalıklarda rol oynadığı yapılan çalışmalarla vurgulanmıştır. Son yıllarda giderek artan sayıdaki çalışmaya rağmen bu hormonların etki mekanizmaları iyi anlaşılamamıştır. Bu derlemede R-spondin-1, nesfatin-1 ve irisin hormonlarının yapısı, sentezi ve biyokimyasal etkilerinden bahsedilmiş, çeşitli hastalıklar üzerine etkileriyle ilgili literatür bilgileri özetlenmiştir.

Keywords

• Hormon
• R-Spondin-1
• Nesfatin-1
• İrisin

Novel Hormones: R-Spondin-1, Nesfatin-1 and Irisin

Abstract

 

The R-spondin family of Wnt modulators draws considerable attention from the ability to increase the β-catenin / Wnt signal activity in various disease processes. Irisin, which is associated with diseases such as metabolic disorders, obesity and diabetes, is another promising hormone in the treatment and monitoring of these diseases. On the other hand, it has been emphasized that nesfatin-1, an anorexigenic hormone, plays a role in psychiatric disorders and neurogenic diseases in addition to obesity and diabetes. Despite the increasing number of
studies in recent years, the mechanism of action of these hormones is not well understood. In this review, the structure, synthesis and biochemical effects of R-spondin-1, nesfatin-1 and irisin hormones are mentioned.

Keywords

• Hormone
• R-Spondin-1
• Nesfatin-1
• Irisin

References

1. Anwar G.M., Yamamah G., Ibrahim A., El-Lebedy D., Farid T.M., Mahmoud R. (2014). Nesfatin-1 in childhood and adolescent obesity and its association with food intake, body composition and insulin resistance. Regulatory peptides, 188, 21-24.
2. Arend R.C., Londono-Joshi A.I., Gangrade A., Katre A.A., Kurpad C., Li Y., Samant R.S., Li P.K., Landen C.N., Yang E.S., Hidalgo B., Alvarez R.D., Straughn J.M., Forero A., Buchsbaum D.J. (2016). Niclosamide and its analogs are potent inhibitors of Wnt/beta-catenin, mTOR and STAT3 signaling in ovarian cancer. Oncotarget, 7 (52), 86803-86815.
3. Argyropoulos G., Harper M.E. (2002). Uncoupling proteins and thermoregulation, J Appl Physiol (1985), 92 (5), 2187-98.
4. Austin S., St-Pierre J. (2012). PGC1alpha and mitochondrial metabolism emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci., 125, 4963-71.
5. Ayada C., Toru U., Korkut Y. (2015). Nesfatin-1 and its effects on different systems. Hippokratia, 19, 4-10.
6. Beckers S., Zegers D., Van Gaal L.F., Van Hul W. (2009). The role of the leptin-melanocortin signalling pathway in the control of food intake. Crit Rev Eukaryot Gene Expr., 19, 267-287.
7. Behrens J., Jerchow B.A., Würtele M., Grimm J., Asbrand C., Wirtz R., Kühl M., Wedlich D., Birchmeier W. (1998) Functional inte raction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science, 280, 596-9.
8. Boone J.D., Arend R.C., Johnston B.E., Cooper S.J., Gilchrist S.A., Oelschlager D.K., Grizzle W.E., McGwin Jr G., Gangrade A., Straughn Jr J.M., Buchsbaum D.J. (2016). Targeting the Wnt/beta-catenin pathway in primary ovarian cancer with the porcupine inhibitor WNT974. Lab. Investig. 96, 249-259.

9. Boström P., Wu J., Jedrychowski M.P., Korde A., Ye L., Lo J.C., Rasbach K.A., Boström E.A., Choi J.H., Long J.Z., Kajimura S., Zingaretti M.C., Vind B.F., Tu H., Cinti S., Højlund K., Gygi S.P., Spiegelman B.M., (2012). A PGC1-α-dependent myokine that drivesbrown-fat-like development of white fat and thermogenesis. Nature, 481, 463-8.
10. Callahan R., Smith G.H. (2008). Common integration sites for MMTV in viral induced mouse mammary tumors. Journal of Mammary Gland Biology and Neoplasia, 13, 309-321.
11. Caruso M., Ferranti F., Scheri K.C., Dobrowolny G., Ciccarone F., Grammatico P., Catizone A., Ricci G. (2015) R-Spondin 1/dickkopf-1/beta-catenin machinery is involved in testicular embryonic angiogenesis. Plos one, 10 (4), 1-25.
12. Castillo-Quan J.I. (2012). From white to brown fat through the PGC-1α-dependent myokine irisin: implications for diabetes and obesity. Dis Model Mech., 5, 293-295.Chen X., Yang J., Evans P.M., Liu C. (2008). Wnt signaling: the good and the bad. Acta Biochim Biophys Sin (Shanghai), 40 (7), 577-94.
13. Cho S.W., Lee E.J., Kim H., Kim S.H., Ahn H.Y., Kim Y.A., Yi K.H., Park D.J., Shin C.S., Ahn S.H., Cho B.Y., Park Y.J. (2013). Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling. Mol Cell Endocrinol., 366, 90-98.
14. Choi Y.K., Kim M.K., Bae K.H., Seo H.A., Jeong J.Y., Lee W.K., Kim J.G., Lee I.K., Park K.G. (2013). Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract., 100, 96-101.
15. Dai H., Li X., He T., Wang Y., Wang Z., et al. (2013). Decreased plasma nesfatin-1 levels in patients with acute myocardial infarction. Peptides, 46, 167-71.
16. Deniz R., Gurates B., Aydin S., Celik H., Sahin I., Baykus Y., Catak Z., Aksoy A., Citil C., Gungor S. (2012) Nesfatin-1 and other hormone alterations in polycystic ovary syndrome. Endocrine, 42 (3), 694-9.
17. Dun S.L., Lyu R.M., Chen Y.H., Chang J.K., Luo J.J., Dun N.J. (2013). Irisin-immunoreactivity in neural and non-neural cells of the rodent. Neuroscience, 240, 155-62.
18. García-Galiano D., Navarro V.M., Roa J., Ruiz-Pino F., Sánchez-Garrido M.A., Pineda R., Castellano J.M., Romero M., Aguilar E., Gaytán F., Diéguez C., Pinilla L., Tena-Sempere M. (2010). The anorexigenic neuropeptide, nesfatin-1, is indispensable for normal puberty onset in the female rat, J Neurosci., 30 (23), 7783-92.
19. Goebel M., Stengel A., Wang L., Lambrecht N.W.G., Taché Y. (2009). Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei. Neurosci Lett., 452, 241-6.
20. Gonzalez R., Shepperd E., Thiruppugazh V., Lohan S., Grey C.L., Chang J.P., Unniappan S. (2012). Nesfatin-1 regulates the hypothalamo-pituitary-ovarian axis of fish. Biol Reprod., 87 (4), 1-11.
21. Handschin C., Spiegelman B.M. (2008). The role of exercise and PGC1alpha in inflammation and chronic disease. Nature, 454, 463-9.
22. Hecksteden A., Wegmann M., Steffen A., Kraushaar J., Morsch A., Ruppenthal S., Kaestner L., Meyer T. (2013). Irisin and exercise training in humans - results from a randomized controlled training trial. BMC Med., 11, 235.
23. Hemlbrecht K., Kispert A., von Wasielewski R., Brabant G. (2011). Identification of a Wnt/β-catenin Signaling Pathway in Human Thyroid Cells. Endocrinology, 142, 5261-5266.
24. Hofmann T., Weibert E., Ahnis A., Obbarius A., Elbelt U., Rose M., Klapp B.F., Stengel A. (2017). Alterations of circulating NUCB2/nesfatin-1 during short term therapeutic improvement of anxiety in obese inpatients. Psychoneuroendocrinology, 79, 107-115.
25. Huh J.Y., Panagiotou G., Mougios V., Brinkoetter M., Vamvini M.T., Schneider B.E., Mantzoros C.S.(2012). 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, 61 (12), 1725-38.
26. Kamata T., Katsube K., Michikawa M., Yamada M., Takada S., Mizusawa H. (2004). R-spondin, a novel gene with thrombospondin type 1 domain, was expressed in the dorsal neural tube and affected in Wnts mutants. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1676, 51-62.
27. Korucu C.Ç., Atay İ.M., Zayıf S.S., Gültekin F. (2018). May nesfatin-1 be a state marker in major depressive disorder with suicidal ideation?. Psychiatry Research, 267, 272-276.
28. Kraemer R.R., Shockett P., Webb N.D., Shah U., Castracane V.D. (2014). A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women. Horm Metab Res., 46 (2), 150-4.
29. Krönke G., Uderhardt S., Kim K.A., Stock M., Scholtysek C. et al. (2010). Rspondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway. Arthritis Rheum, 62 (8), 2303-12.
30. Kuchenbaecker K.B., Ramus S.J., Tyrer J., Lee A., Shen H.C., Beesley J. et al. (2015). Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nat Genet., 47 (2), 164-71,
31. Lecker S.H., Zavin A., Cao P., Arena R., Allsup K., Daniels K.M., Joseph J., Schulze P.C., Forman D.E., (2012). Expression of the irisin precursor FNDC5 in skeletal muscle correlates with aerobic exercise performance in patients with heart failure. Circ Heart Fail., 5 (6), 812-818.
32. Liu Q., Zhao Y., Xing H., Li L., Li R., Dai J., Li Q., Fang S. (2019). The role of R-spondin 1 through activating Wnt/β-catenin in the growth, survival and migration of ovarian cancer cells. Gene., 689, 124-130.
33. Liu Z., Habener J.F. (2008). Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic beta cell proliferation. Journal of Biological Chemistry, 283 (13), 8723-8735.
34. Liu Z., Kakudo K., Bai Y., Li Y., Ozaki T., Miyauchi A., Taniquchi E., Mori I. (2011). Loss of cellular polarity/cohesive¬ness in the invasive front of papillary thyroid carcinoma, a novel predictor for lymph node metastasis; possible morphological indicator of epithelial mesenchymal transition. J Clin Pathol., 64, 325-329.
35. Lowther W., Wiley K., Smith G.H., Callahan R. (2005). A new common integration site, Int7, for the mouse mammary tumor virus in mouse mammary tumors identifies a gene whose product has furin-like and thrombospondin-like sequences. Journal of Virolog, 79, 10093-10096.
36. Lu W., Kim K.A., Liu J., Abo A., Feng X., Cao X., Li Y. (2008). R-spondin1 synergizes with Wnt3A in inducing osteoblast differentiation and osteoprotegerin expression. FEBS Letters, 582 (5), 643-650.
37. Mahgoub M.O., D'Souza C., Al Darmaki R.S.M.H., Baniyas M.M.Y.H., Adeghate E. (2018). An update on the role of irisin in the regulation of endocrine and metabolic functions. Peptides, 104, 11-23.
38. Mikels A.J., Nusse R. (2006). Wnts as ligands: processing, secretion and reception. Oncogene, 25, 7461-8,
39. Mirzaei K., Hossein-nezhad A., Keshavarz S.A., Koohdani F., Eshraghian M.R., Saboor-Yaraghi A.A., Hosseini S., Chamari M., Zareei M., Djalali M. (2015). Association of nesfatin-1 level with body composition, dietary intake and resting metabolic rate in obese and morbid obese subjects. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 9 (4), 292-298.
40. Moraes C., Leal V.O., Marinho S.M., Barroso S.G., Roch G.S., Boaventura G.T., Mafra D. (2013). Resistance exercise training does not affect plasma irisin levels of hemodialysis patients. Horm Metab Res., 45 (12), 900-4.
41. Moreno-Navarrete J.M., Ortega F., Serrano M., Guerra E., Pardo G., Tinahones F., Ricart W., Fernández-Real J.M. (2013). Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab., 98 (4), 769-778.
42. Nakata M., Manaka K., Yamamoto S., Mori M., Yada T. (2011). Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca (2+) influx through L-type channels in mouse islet β-cells. Endocr J., 58 (4), 305-13.
43. Oh-I S., Shimizu H., Satoh T., Okada S., Adachi S., Inoue K., Eguchi H., Yamamoto M., Imaki T., Hashimoto K., Tsuchiya T., Monden T., Horiguchi K., Yamada M., Mori M. (2006). Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature, 443, 709-712.
44. Ootani A., Li X., Sangiorgi E., Ho Q.T., Ueno H., Toda S., Sugihara H., Fujimoto K., Weissman I.L., Capecchi M.R., Kuo C.J. (2009). Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nature Medicine, 15 (6), 701-706.
45. Pałasz A., Janas-Kozik M., Borrow A., Arias-Carrión O., Worthington J.J. (2018). The potential role of the novel hypothalamic neuropeptides nesfatin-1, phoenixin, spexin and kisspeptin in the pathogenesis of anxiety and anorexia nervosa. Neurochemistry international, 113, 120-136.
46. Pekkala S., Wiklund P.K., Hulmi J.J., Ahtiainen J.P., Horttanainen M., Pollanen E., Makela K.A., Kainulainen H., Hakkinen K., Nyman K., Alen M., Herzig K.H., Cheng S. (2013). Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? J Physiol., 591, 5393-400.
47. Rodgers R.J., Tschöp M.H., Wilding J.P.H. (2012) Anti-obesity drugs: past, present and future, Dis Model Mech., 5, 621- 626.
48. Ruan Q., Huang Y., Yang L., Ruan J., Gu W., Zhang X., Zhang Y., Zhang W., Yu Z. (2019). The effects of both age and sex on irisin levels in paired plasma and cerebrospinal fluid in healthy humans. Peptides, 113, 41-51.
49. Rulifson I.C., Karnik S.K., Heiser P.W., ten Berge D., Chen H., Gu X., Taketo M.M., Nusse R., Hebrok M., Kim S.K. (2007). Wnt signaling regulates pancreatic beta cell proliferation. Proceedings of the National Academy of Sciences of the United States of America, 104 (15), 6247-6252.
50. Sato T., Vries R.G., Snippert H.J.,van de Wetering M., Barker N., Stange D.E., van Es J.H., Abo A., Kujala P., Peters P.J., Clevers H. (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 459 (7244), 262–265.
51. Seale P., Bjork B, Yang W, Kajimura S, Chin S., Kuang S, Scimè A, Devarakonda S, Conroe H.M., Erdjument-Bromage H., Tempst P., Rudnicki M.A., Beier D.R., Spiegelman B.M. (2008). PRDM16 controls a brown fat/skeletal muscle switch. Nature, 454, 961-967.
52. Starr T.K., Allaei R., Silverstein K.A., Staggs R.A., Sarver A.L., Bergemann T.L., Gupta M., O'Sullivan M.G., Matise I., Dupuy A.J., Collier L.S., Powers S., Oberg A.L., Asmann Y.W., Thibodeau S.N., Tessarollo L., Copeland N.G., Jenkins N.A., Cormier R.T., Largaespada D.A. (2009). A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science, 323, 1747-1750.
53. Stengel A, Taché Y, 2011. Minireview: nesfatin-1 an emerging new player in the brain-gut, endocrine, and metabolic axis. Endocrinology, 152 (11), 4033-8.
54. Tanır H.G., Demirezen Ş. (2009). Wnt sinyal yolunun biyolojisi ve bu yolda görev alan biyomoleküller. Türkiye Klinikleri J Med Sci., 29 (5), 1292-7.
55. Theodorou V., Kimm M.A., Boer M., Wessels L., Theelen W., Jonkers J., Hilkens J. (2007). MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer. Nature Genetics, 39, 759-769.
56. Timmons J.A., Baar K., Davidsen P.K., Atherton P.J. (2012). Is irisin a human exercise gene? Nature, 488, 9-10.
57. Ünal K., Yüksel R.N., Turhan T., Sezer S., Yaylaci E.T. (2018). The association of serum nesfatin-1 and ghrelin levels with metabolic syndrome in patients with schizophrenia. Psychiatry research, 261, 45-49.
58. Villarroya F. (2012). Irisin, Turning Up the Heat. Cell Metab., 15( 3), 277-8.
59. Wong V.S., Yeung A., Schultz W., Brubaker P.L. (2010). R-spondin-1 is a novel β-Cell growth factor and insulin secretagogue. The Journal of Biological Chemistry, 285 (28), 21292-21302.
60. Yan B., Shi X., Zhang H., Pan L., Ma Z., Liu S., Liu Y., Li X., Yang S., Li Z. (2014). Association of serum irisin with metabolic syndrome in obese Chinese adults. Plos One, 9 (4), 1-10.
61. Zeng X., Huang H., Tamai K., Zhang X., Harada Y., Yokota, C. et al. (2008). Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishe-velled and axin functions. Development, 135 (2), 367-75.