Anti-inflammatory effects of irisin in inflammatory diseases_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DU Jie ¹ , ZHANG Xuedong ² , LI Zhixiong ¹ , ZHANG Rui ³ ,  LU Yan ⁴ ,  CHAI Chen ^1,5

1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;
2. Shanxi Medical University, Taiyuan 030000, P. R. China;
3. Northwest Minzu University, Lanzhou 730000, P. R. China;
4. Department of Clinical Laboratory, 96604 Military Hospital of Chinese People’s Liberation Army, Lanzhou 730030, P. R. China;
5. People’s Hospital of Suzhou New District, Suzhou, Jiangsu 215000, P. R. China;

Corresponding author：

LU Yan, Email: lu73free@aliyun.com; CHAI Chen, Email: chasechai@126.com

Keywords：

irisin; inflammation; inflammatory factor; signal pathway

DOI：

10.7507/1007-9424.201909038

Video：

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Objective To summarize the anti-inflammatory effects of irisin in inflammatory diseases.Method The relevant literatures at home and abroad in recent years were systematically searched and read to review the anti-inflammatory effects of irisin in the inflammatory diseases.Results The irisin was widely distributed in the body and played a physiological role in inducing the browning of white adipocytes, improving energy metabolism and glucose utilization. A grow body of evidences demonstrated that the irisin exerted the anti-inflammatory effects by inhibiting increased pro-inflammatory cytokines and tumor necrosis factor-α, antagonizing apoptosis and activation of nuclear factor-κB, and improving tissue damage in many inflammatory diseases, such as acute lung injury, inflammatory bowel disease, septic cardiomyopathy, acute pancreatitis, nonalcoholic fatty liver disease, and malignant tumors.Conclusions Irisin plays an important anti-inflammatory role in pathogenesis of inflammatory diseases. Irisin is considered as a promising candidate biomarker for diagnosis and prognosis of inflammatory diseases, and a novel target for treatment of inflammatory diseases.

Citation： DU Jie, ZHANG Xuedong, LI Zhixiong, ZHANG Rui, LU Yan, CHAI Chen. Anti-inflammatory effects of irisin in inflammatory diseases. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(4): 499-503. doi: 10.7507/1007-9424.201909038 Copy

1.	Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 2012, 481(7382): 463-468.
2.	Ugur K, Aydin S, Kuloglu T, et al. Comparison of irisin hormone expression between thyroid cancer tissues and oncocytic variant cells. Cancer Manag Res, 2019, 11: 2595-2603.
3.	Shen S, Liao Q, Zhang T, et al. Myricanol modulates skeletal muscle-adipose tissue crosstalk to alleviate high-fat diet-induced obesity and insulin resistance. Br J Pharmacol, 2019, 176(20): 3983-4001.
4.	Metwally M, Bayoumi A, Romero-Gomez M, et al. A polymorphism in the Irisin-encoding gene (FNDC5) associates with hepatic steatosis by differential miRNA binding to the 3′UTR. J Hepatol, 2019, 70(3): 494-500.
5.	Li H, Shen J, Wu T, et al. Irisin is controlled by farnesoid X receptor and regulates cholesterol homeostasis. Front Pharmacol, 2019, 10: 548.
6.	Kuloğlu T, Artaş G, Yardim M, et al. Immunostaining characteristics of irisin in benign and malignant renal cancers. Biotech Histochem, 2019, 94(6): 435-441.
7.	Liu J, Song N, Huang Y, et al. Irisin inhibits pancreatic cancer cell growth via the AMPK-mTOR pathway. Sci Rep, 2018, 8(1): 15247.
8.	Peng H, Wang Q, Lou T, et al. Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys. Nat Commun, 2017, 8(1): 1493.
9.	Elizondo-Montemayor L, Mendoza-Lara G, Gutierrez-DelBosque G, et al. Relationship of circulating irisin with body composition, physical activity, and cardiovascular and metabolic disorders in the pediatric population. Int J Mol Sci, 2018, 19(12): pii: E3727.
10.	Gizaw M, Anandakumar P, Debela T. A review on the role of irisin in insulin resistance and type 2 diabetes mellitus. J Pharmacopuncture, 2017, 20(4): 235-242.
11.	Huh JY, Panagiotou G, Mougios V, 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): 1725-1738.
12.	Aydin S, Kuloglu T, Aydin S, et al. A comprehensive immunohistochemical examination of the distribution of the fat-burning protein irisin in biological tissues. Peptides, 2014, 61: 130-136.
13.	Aydin S, Aydin S, Kuloglu T, et al. Alterations of irisin concentrations in saliva and serum of obese and normal-weight subjects, before and after 45 min of a Turkish bath or running. Peptides, 2013, 50: 13-18.
14.	Piya MK, Harte AL, Sivakumar K, et al. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. Am J Physiol Endocrinol Metab, 2014, 306(5): E512-E518.
15.	Aydin S, Kuloglu T, Aydin S. Copeptin, adropin and irisin concentrations in breast milk and plasma of healthy women and those with gestational diabetes mellitus. Peptides, 2013, 47: 66-70.
16.	Hofmann T, Elbelt U, Stengel A. Irisin as a muscle-derived hormone stimulating thermogenesis-a critical update. Peptides, 2014, 54: 89-100.
17.	Aydin S, Kuloglu T, Aydin S, et al. Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: cardiac muscle produces more irisin than skeletal muscle. Peptides, 2014, 52: 68-73.
18.	Gür FM, Timurkaan S, Gençer Tarakçi B, et al. Identification of immunohistochemical localization of irisin in the dwarf hamster (Phodopus roborovskii) tissues. Anat Histol Embryol, 2018, 47(2): 174-179.
19.	Komolka K, Albrecht E, Schering L, et al. Locus characterization and gene expression of bovine FNDC5: is the myokine irisin relevant in cattle? PLoS One, 2014, 9(1): e88060.
20.	Wu J, Boström P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell, 2012, 150(2): 366-376.
21.	Moreno-Perez O, Reyes-Garcia R, Muñoz-Torres M, et al. High Irisin levels in nondiabetic HIV-infected males are associated with insulin resistance, nonalcoholic fatty liver disease, and subclinical atherosclerosis. Clin Endocrinol (Oxf), 2018, 89(4): 414-423.
22.	Sanchis-Gomar F, Perez-Quilis C. The p38-PGC-1α-irisin-betatrophin axis: Exploring new pathways in insulin resistance. Adipocyte, 2014, 3(1): 67-68.
23.	Colaianni G, Cuscito C, Mongelli T, et al. Irisin enhances osteoblast differentiation in vitro. Int J Endocrinol, 2014, 2014: 902186.
24.	Anastasilakis AD, Polyzos SA, Makras P, et al. Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos Int, 2014, 25(5): 1633-1642.
25.	Lourenco MV, Frozza RL, de Freitas GB, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. Nat Med, 2019, 25(1): 165-175.
26.	Johnson ER, Matthay MA. Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv, 2010, 23(4): 243-252.
27.	Shao L, Meng D, Yang F, et al. Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells. Biochem Biophys Res Commun, 2017, 487(2): 194-200.
28.	Mozaffari S, Abdolghaffari AH, Nikfar S, Abdollahi M. Pregnancy outcomes in women with inflammatory bowel disease following exposure to thiopurines and antitumor necrosis factor drugs: a systematic review with meta-analysis. Hum Exp Toxicol, 2015, 34(5): 445-459.
29.	Mozaffari S, Abdollahi M. Melatonin, a promising supplement in inflammatory bowel disease: a comprehensive review of evidences. Curr Pharm Des, 2011, 17(38): 4372-4378.
30.	Mazur-Bialy AI, Bilski J, Wojcik D, et al. Beneficial effect of voluntary exercise on experimental colitis in mice fed a high-fat diet: the role of irisin, adiponectin and proinflammatory biomarkers. Nutrients, 2017, 9(4): pii: E410.
31.	Bilski J, Mazur-Bialy AI, Brzozowski B, et al. Moderate exercise training attenuates the severity of experimental rodent colitis: the importance of crosstalk between adipose tissue and skeletal muscles. Mediators Inflamm, 2015, 2015: 605071.
32.	Narayanan SA, Metzger CE, Bloomfield SA, et al. Inflammation-induced lymphatic architecture and bone turnover changes are ameliorated by irisin treatment in chronic inflammatory bowel disease. FASEB J, 2018, 32(9): 4848-4861.
33.	Tan Y, Ouyang H, Xiao X, et al. Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway. Cell Stress Chaperones, 2019, 24(3): 595-608.
34.	陈莎燕, 赵琳, 孙兰菊, 等. 血清鸢尾素检测对重型急性胰腺炎诊断的价值. 广东医学, 2017, 38(23): 3617-3619.
35.	Chen S, Wang L, Gao X, et al. Characterization of serum irisin in patients with severe acute pancreatitis. Eur J Gastroenterol Hepatol, 2019, 31(8): 985-991.
36.	Ren Y, Qiu M, Zhang J, et al. Low serum irisin concentration is associated with poor outcomes in patients with acute pancreatitis, and irisin administration protects against experimental acute pancreatitis. Antioxid Redox Signal, 2019, 31(11): 771-785.
37.	Tilg H. Adipocytokines in nonalcoholic fatty liver disease: key players regulating steatosis, inflammation and fibrosis. Curr Pharm Des, 2010, 16(17): 1893-1895.
38.	Polyzos SA, Kountouras J, Anastasilakis AD, et al. Irisin in patients with nonalcoholic fatty liver disease. Metabolism, 2014, 63(2): 207-217.
39.	Park MJ, Kim DI, Choi JH, et al. New role of irisin in hepatocytes: The protective effect of hepatic steatosis in vitro. Cell Signal, 2015, 27(9): 1831-1839.
40.	Maalouf GE, El Khoury D. Exercise-induced irisin, the fat browning myokine, as a potential anticancer agent. J Obes, 2019, 2019: 6561726.
41.	Gaggini M, Cabiati M, Del Turco S, et al. Increased FNDC5/Irisin expression in human hepatocellular carcinoma. Peptides, 2017, 88: 62-66.
42.	Gannon NP, Vaughan RA, Garcia-Smith R, et al. Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro. Int J Cancer, 2015, 136(4): E197-E202.
43.	Zhang D, Zhang P, Li L, et al. Irisin functions to inhibit malignant growth of human pancreatic cancer cells via downregulation of the PI3K/AKT signaling pathway. Onco Targets Ther, 2019, 12: 7243-7249.
44.	Shao L, Li H, Chen J, et al. Irisin suppresses the migration, proliferation, and invasion of lung cancer cells via inhibition of epithelial-to-mesenchymal transition. Biochem Biophys Res Commun, 2017, 485(3): 598-605.
45.	Liu J, Huang Y, Liu Y, et al. Irisin enhances doxorubicin-induced cell apoptosis in pancreatic cancer by inhibiting the PI3K/AKT/NF-κB pathway. Med Sci Monit, 2019, 25: 6085-6096.
46.	Shi G, Tang N, Qiu J, et al. Irisin stimulates cell proliferation and invasion by targeting the PI3K/AKT pathway in human hepatocellular carcinoma. Biochem Biophys Res Commun, 2017, 493(1): 585-591.
47.	Moon HS, Mantzoros CS. Regulation of cell proliferation and malignant potential by irisin in endometrial, colon, thyroid and esophageal cancer cell lines. Metabolism, 2014, 63(2): 188-193.
48.	Altay DU, Keha EE, Karagüzel E, et al. The diagnostic value of FNDC5/irisin in renal cell cancer. Int Braz J Urol, 2018, 44(4): 734-739.
49.	王珅, 廖静雯, 尹洪刚, 等. 鸢尾素的心血管保护作用及其在运动领域的研究进展. 生理学报, 2019, 71(3): 478-484.

1. Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 2012, 481(7382): 463-468.
2. Ugur K, Aydin S, Kuloglu T, et al. Comparison of irisin hormone expression between thyroid cancer tissues and oncocytic variant cells. Cancer Manag Res, 2019, 11: 2595-2603.
3. Shen S, Liao Q, Zhang T, et al. Myricanol modulates skeletal muscle-adipose tissue crosstalk to alleviate high-fat diet-induced obesity and insulin resistance. Br J Pharmacol, 2019, 176(20): 3983-4001.
4. Metwally M, Bayoumi A, Romero-Gomez M, et al. A polymorphism in the Irisin-encoding gene (FNDC5) associates with hepatic steatosis by differential miRNA binding to the 3′UTR. J Hepatol, 2019, 70(3): 494-500.
5. Li H, Shen J, Wu T, et al. Irisin is controlled by farnesoid X receptor and regulates cholesterol homeostasis. Front Pharmacol, 2019, 10: 548.
6. Kuloğlu T, Artaş G, Yardim M, et al. Immunostaining characteristics of irisin in benign and malignant renal cancers. Biotech Histochem, 2019, 94(6): 435-441.
7. Liu J, Song N, Huang Y, et al. Irisin inhibits pancreatic cancer cell growth via the AMPK-mTOR pathway. Sci Rep, 2018, 8(1): 15247.
8. Peng H, Wang Q, Lou T, et al. Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys. Nat Commun, 2017, 8(1): 1493.
9. Elizondo-Montemayor L, Mendoza-Lara G, Gutierrez-DelBosque G, et al. Relationship of circulating irisin with body composition, physical activity, and cardiovascular and metabolic disorders in the pediatric population. Int J Mol Sci, 2018, 19(12): pii: E3727.
10. Gizaw M, Anandakumar P, Debela T. A review on the role of irisin in insulin resistance and type 2 diabetes mellitus. J Pharmacopuncture, 2017, 20(4): 235-242.
11. Huh JY, Panagiotou G, Mougios V, 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): 1725-1738.
12. Aydin S, Kuloglu T, Aydin S, et al. A comprehensive immunohistochemical examination of the distribution of the fat-burning protein irisin in biological tissues. Peptides, 2014, 61: 130-136.
13. Aydin S, Aydin S, Kuloglu T, et al. Alterations of irisin concentrations in saliva and serum of obese and normal-weight subjects, before and after 45 min of a Turkish bath or running. Peptides, 2013, 50: 13-18.
14. Piya MK, Harte AL, Sivakumar K, et al. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. Am J Physiol Endocrinol Metab, 2014, 306(5): E512-E518.
15. Aydin S, Kuloglu T, Aydin S. Copeptin, adropin and irisin concentrations in breast milk and plasma of healthy women and those with gestational diabetes mellitus. Peptides, 2013, 47: 66-70.
16. Hofmann T, Elbelt U, Stengel A. Irisin as a muscle-derived hormone stimulating thermogenesis-a critical update. Peptides, 2014, 54: 89-100.
17. Aydin S, Kuloglu T, Aydin S, et al. Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: cardiac muscle produces more irisin than skeletal muscle. Peptides, 2014, 52: 68-73.
18. Gür FM, Timurkaan S, Gençer Tarakçi B, et al. Identification of immunohistochemical localization of irisin in the dwarf hamster (Phodopus roborovskii) tissues. Anat Histol Embryol, 2018, 47(2): 174-179.
19. Komolka K, Albrecht E, Schering L, et al. Locus characterization and gene expression of bovine FNDC5: is the myokine irisin relevant in cattle? PLoS One, 2014, 9(1): e88060.
20. Wu J, Boström P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell, 2012, 150(2): 366-376.
21. Moreno-Perez O, Reyes-Garcia R, Muñoz-Torres M, et al. High Irisin levels in nondiabetic HIV-infected males are associated with insulin resistance, nonalcoholic fatty liver disease, and subclinical atherosclerosis. Clin Endocrinol (Oxf), 2018, 89(4): 414-423.
22. Sanchis-Gomar F, Perez-Quilis C. The p38-PGC-1α-irisin-betatrophin axis: Exploring new pathways in insulin resistance. Adipocyte, 2014, 3(1): 67-68.
23. Colaianni G, Cuscito C, Mongelli T, et al. Irisin enhances osteoblast differentiation in vitro. Int J Endocrinol, 2014, 2014: 902186.
24. Anastasilakis AD, Polyzos SA, Makras P, et al. Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos Int, 2014, 25(5): 1633-1642.
25. Lourenco MV, Frozza RL, de Freitas GB, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. Nat Med, 2019, 25(1): 165-175.
26. Johnson ER, Matthay MA. Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv, 2010, 23(4): 243-252.
27. Shao L, Meng D, Yang F, et al. Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells. Biochem Biophys Res Commun, 2017, 487(2): 194-200.
28. Mozaffari S, Abdolghaffari AH, Nikfar S, Abdollahi M. Pregnancy outcomes in women with inflammatory bowel disease following exposure to thiopurines and antitumor necrosis factor drugs: a systematic review with meta-analysis. Hum Exp Toxicol, 2015, 34(5): 445-459.
29. Mozaffari S, Abdollahi M. Melatonin, a promising supplement in inflammatory bowel disease: a comprehensive review of evidences. Curr Pharm Des, 2011, 17(38): 4372-4378.
30. Mazur-Bialy AI, Bilski J, Wojcik D, et al. Beneficial effect of voluntary exercise on experimental colitis in mice fed a high-fat diet: the role of irisin, adiponectin and proinflammatory biomarkers. Nutrients, 2017, 9(4): pii: E410.
31. Bilski J, Mazur-Bialy AI, Brzozowski B, et al. Moderate exercise training attenuates the severity of experimental rodent colitis: the importance of crosstalk between adipose tissue and skeletal muscles. Mediators Inflamm, 2015, 2015: 605071.
32. Narayanan SA, Metzger CE, Bloomfield SA, et al. Inflammation-induced lymphatic architecture and bone turnover changes are ameliorated by irisin treatment in chronic inflammatory bowel disease. FASEB J, 2018, 32(9): 4848-4861.
33. Tan Y, Ouyang H, Xiao X, et al. Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway. Cell Stress Chaperones, 2019, 24(3): 595-608.
34. 陈莎燕, 赵琳, 孙兰菊, 等. 血清鸢尾素检测对重型急性胰腺炎诊断的价值. 广东医学, 2017, 38(23): 3617-3619.
35. Chen S, Wang L, Gao X, et al. Characterization of serum irisin in patients with severe acute pancreatitis. Eur J Gastroenterol Hepatol, 2019, 31(8): 985-991.
36. Ren Y, Qiu M, Zhang J, et al. Low serum irisin concentration is associated with poor outcomes in patients with acute pancreatitis, and irisin administration protects against experimental acute pancreatitis. Antioxid Redox Signal, 2019, 31(11): 771-785.
37. Tilg H. Adipocytokines in nonalcoholic fatty liver disease: key players regulating steatosis, inflammation and fibrosis. Curr Pharm Des, 2010, 16(17): 1893-1895.
38. Polyzos SA, Kountouras J, Anastasilakis AD, et al. Irisin in patients with nonalcoholic fatty liver disease. Metabolism, 2014, 63(2): 207-217.
39. Park MJ, Kim DI, Choi JH, et al. New role of irisin in hepatocytes: The protective effect of hepatic steatosis in vitro. Cell Signal, 2015, 27(9): 1831-1839.
40. Maalouf GE, El Khoury D. Exercise-induced irisin, the fat browning myokine, as a potential anticancer agent. J Obes, 2019, 2019: 6561726.
41. Gaggini M, Cabiati M, Del Turco S, et al. Increased FNDC5/Irisin expression in human hepatocellular carcinoma. Peptides, 2017, 88: 62-66.
42. Gannon NP, Vaughan RA, Garcia-Smith R, et al. Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro. Int J Cancer, 2015, 136(4): E197-E202.
43. Zhang D, Zhang P, Li L, et al. Irisin functions to inhibit malignant growth of human pancreatic cancer cells via downregulation of the PI3K/AKT signaling pathway. Onco Targets Ther, 2019, 12: 7243-7249.
44. Shao L, Li H, Chen J, et al. Irisin suppresses the migration, proliferation, and invasion of lung cancer cells via inhibition of epithelial-to-mesenchymal transition. Biochem Biophys Res Commun, 2017, 485(3): 598-605.
45. Liu J, Huang Y, Liu Y, et al. Irisin enhances doxorubicin-induced cell apoptosis in pancreatic cancer by inhibiting the PI3K/AKT/NF-κB pathway. Med Sci Monit, 2019, 25: 6085-6096.
46. Shi G, Tang N, Qiu J, et al. Irisin stimulates cell proliferation and invasion by targeting the PI3K/AKT pathway in human hepatocellular carcinoma. Biochem Biophys Res Commun, 2017, 493(1): 585-591.
47. Moon HS, Mantzoros CS. Regulation of cell proliferation and malignant potential by irisin in endometrial, colon, thyroid and esophageal cancer cell lines. Metabolism, 2014, 63(2): 188-193.
48. Altay DU, Keha EE, Karagüzel E, et al. The diagnostic value of FNDC5/irisin in renal cell cancer. Int Braz J Urol, 2018, 44(4): 734-739.
49. 王珅, 廖静雯, 尹洪刚, 等. 鸢尾素的心血管保护作用及其在运动领域的研究进展. 生理学报, 2019, 71(3): 478-484.

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