Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb 2;13(3):277.
doi: 10.3390/cells13030277.

The Role of FNDC5/Irisin in Cardiovascular Disease

Maciej Grzeszczuk  1 , Piotr Dzięgiel  1   2 , Katarzyna Nowińska  1
Affiliations
Review

The Role of FNDC5/Irisin in Cardiovascular Disease

Maciej Grzeszczuk et al. Cells. .

Abstract

Disorders of cardiomyocyte metabolism play a crucial role in many cardiovascular diseases, such as myocardial infarction, heart failure and ischemia-reperfusion injury. In myocardial infarction, cardiomyocyte metabolism is regulated by mitochondrial changes and biogenesis, which allows energy homeostasis. There are many proteins in cells that regulate and control metabolic processes. One of them is irisin (Ir), which is released from the transmembrane protein FNDC5. Initial studies indicated that Ir is a myokine secreted mainly by skeletal muscles. Further studies showed that Ir was also present in various tissues. However, its highest levels were observed in cardiomyocytes. Ir is responsible for many processes, including the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT) by increasing the expression of thermogenin (UCP1). In addition, Ir affects mitochondrial biogenesis. Therefore, the levels of FNDC5/Ir in the blood and myocardium may be important in cardiovascular disease. This review discusses the current knowledge about the role of FNDC5/Ir in cardiovascular disease.

Keywords: FNDC5; fibronectin type III domain-containing protein 5; irisin; myocardial infarction.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Structure of the FNDC5 protein based on the spectrometric analysis and the mechanism of Ir release as modified from Young et al. [26].
Figure 2
Figure 2
Effect of irisin on the heart muscle after physical activity. During physical activity, muscles release irisin, which affects the browning process of WAT. The protective effect is achieved through the secretion of the fibroblast growth factor (FGF21), adiponectin (exhibiting anti-inflammatory and anti-atherosclerotic effects), nerve growth factors responsible for the regulation of neuronal growth and survival, and free fatty acids [55].
Figure 3
Figure 3
Effect of irisin (Ir) on endothelial cells. Increase in the level of active phosphorylated ERK kinase (P-ERK). Higher Ir levels increase the expression of matrix metalloproteinase 2 (MMP2) and 9 (MMP9) mRNA, promote endothelial cell proliferation and increase endothelial cell migration.
Figure 4
Figure 4
Effect of Irisin (Ir) on cardiomyocytes. Ir affects cardiomyocytes in hypoxia and reoxygenation, affects cardiomyocytes in diabetic cardiomyopathy, and demonstrates the inhibitory effect on cardiomyocyte hypertrophy.
Figure 5
Figure 5
Changes in serum Irisin (Ir) levels in patients with acute myocardial infarction (MI) based on Aydin et al. [79]; changes in Ir levels in ng/mL over time after MI.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zhu D., Wang H., Zhang J., Zhang X., Xin C., Zhang F., Lee Y., Zhang L., Lian K., Yan W., et al. Irisin Improves Endothelial Function in Type 2 Diabetes through Reducing Oxidative/Nitrative Stresses. J. Mol. Cell Cardiol. 2015;87:138–147. doi: 10.1016/j.yjmcc.2015.07.015. - DOI - PubMed
    1. Huh J.Y., Panagiotou G., Mougios V., Brinkoetter M., Vamvini M.T., Schneider B.E., Mantzoros C.S. 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;61:1725–1738. doi: 10.1016/j.metabol.2012.09.002. - DOI - PMC - PubMed
    1. Kuloglu T., Aydin S., Eren M.N., Yilmaz M., Sahin I., Kalayci M., Sarman E., Kaya N., Yilmaz O.F., Turk A., et al. Irisin: A Potentially Candidate Marker for Myocardial Infarction. Peptides. 2014;55:85–91. doi: 10.1016/j.peptides.2014.02.008. - DOI - PubMed
    1. Liu J.J., Wong M.D.S., Toy W.C., Tan C.S.H., Liu S., Ng X.W., Tavintharan S., Sum C.F., Lim S.C. Lower Circulating Irisin Is Associated with Type 2 Diabetes Mellitus. J. Diabetes Complicat. 2013;27:365–369. doi: 10.1016/j.jdiacomp.2013.03.002. - DOI - PubMed
    1. Roca-Rivada A., Castelao C., Senin L.L., Landrove M.O., Baltar J., Crujeiras A.B., Seoane L.M., Casanueva F.F., Pardo M. FNDC5/Irisin Is Not Only a Myokine but Also an Adipokine. PLoS ONE. 2013;8:e60563. doi: 10.1371/journal.pone.0060563. - DOI - PMC - PubMed

MeSH terms