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  • Review Article
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Physiology and role of irisin in glucose homeostasis

Nature Reviews Endocrinology volume 13, pages 324–337 (2017)Cite this article

Subjects

Key Points

  • Irisin is secreted primarily by muscle and in small amounts by adipose tissue

  • Irisin improves glucose homeostasis, lipid profile and metabolic parameters in animals and acts on adipose tissue by inducing 'browning', as well as on muscle and liver

  • Inconsistencies in published data regarding the circulating levels of irisin highlight the need for accurate methods for irisin measurement and for improved study design

  • Levels of irisin are increased in states of obesity and decreased in patients with type 2 diabetes mellitus (T2DM)

  • Future studies should try to identify the irisin receptor and to investigate the effects of irisin on the endocrine pancreas and appetite centres in the brain; prospective clinical studies should investigate whether irisin is a predictive marker for insulin resistance, T2DM or the metabolic syndrome

Abstract

Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Consequently, several studies attempted to characterize the role of irisin in glucose regulation, but contradictory results have been reported, and even the existence of this hormone has been questioned. In this Review, we present the current knowledge on the physiology of irisin and its role in glucose homeostasis. We describe the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement of irisin. We also discuss the direct effects of irisin on glucose regulatory mechanisms in different organs, the indirect effects and interactions with other hormones, and the important open questions with regard to irisin in those organs. Finally, we present the results from animal interventional studies and from human clinical studies investigating the association of irisin with obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome.

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Figure 1: Candidate signalling pathways of irisin in adipocytes.
Figure 2: Candidate signalling pathways of irisin in myocytes.
Figure 3: Candidate signalling pathways of irisin in hepatocytes.
Figure 4: Effects of irisin on glucose homeostasis.

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Acknowledgements

C.S.M. is supported by US National Institutes of Health (NIH DK081913). J.M.F-R. is supported by Instituto Salud Carlos III (http://www.isciii.es); Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERobn) (http://www.ciberobn.es); Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (www.gencat.cat/agaur/) (2015FI_B00570); and Fondo Europeo de Desarrollo Regional (FEDER).

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, 02215, Massachusetts, USA

    Nikolaos Perakakis, Georgios A. Triantafyllou & Christos S. Mantzoros

  2. Department of Endocrinology, Hospital of Girona Doctor Josep Trueta, University of Girona, Emili Grahit Street, 17003, Girona, Spain

    José Manuel Fernández-Real

  3. Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERobn), Avinguda de França, 17007, Girona, Spain

    José Manuel Fernández-Real

  4. College of Pharmacy, Chonnam National University, 77, Yongbong-ro, Buk-gu, 61186, Gwangju, South Korea

    Joo Young Huh

  5. Department of Family Medicine, Hallym University Sacred Heart Hospital, Hallym University, 431070, Gyeonggi-do, South Korea

    Kyung Hee Park

  6. Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg, Faculty of Medicine, University of Freiburg, 55 Hugstetter Street, 79106, Freiburg, Germany

    Jochen Seufert

  7. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, 150 South Huntington Avenue, Boston, 02130, Massachusetts, USA

    Christos S. Mantzoros

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  1. Nikolaos Perakakis
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  2. Georgios A. Triantafyllou
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  4. Joo Young Huh
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  5. Kyung Hee Park
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Contributions

N.P. researched data for the article and wrote the manuscript. G.A.T. researched data for the article, wrote the manuscript and edited the article before submission. J.M.F-R., J.Y.H., K.H.P., J.S. and C.S.M. contributed to discussion of the content, wrote parts of the article and reviewed and/or edited the article before submission.

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Correspondence to Nikolaos Perakakis or Christos S. Mantzoros.

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Perakakis, N., Triantafyllou, G., Fernández-Real, J. et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol 13, 324–337 (2017). https://doi.org/10.1038/nrendo.2016.221

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