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Progress and Challenges in the Biology of FNDC5 and Irisin.

Publication ,  Journal Article
Maak, S; Norheim, F; Drevon, CA; Erickson, HP
Published in: Endocr Rev
July 16, 2021

In 2002, a transmembrane protein-now known as FNDC5-was discovered and shown to be expressed in skeletal muscle, heart, and brain. It was virtually ignored for 10 years, until a study in 2012 proposed that, in response to exercise, the ectodomain of skeletal muscle FNDC5 was cleaved, traveled to white adipose tissue, and induced browning. The wasted energy of this browning raised the possibility that this myokine, named irisin, might mediate some beneficial effects of exercise. Since then, more than 1000 papers have been published exploring the roles of irisin. A major interest has been on adipose tissue and metabolism, following up the major proposal from 2012. Many studies correlating plasma irisin levels with physiological conditions have been questioned for using flawed assays for irisin concentration. However, experiments altering irisin levels by injecting recombinant irisin or by gene knockout are more promising. Recent discoveries have suggested potential roles of irisin in bone remodeling and in the brain, with effects potentially related to Alzheimer's disease. We discuss some discrepancies between research groups and the mechanisms that are yet to be determined. Some important questions raised in the initial discovery of irisin, such as the role of the mutant start codon of human FNDC5 and the mechanism of ectodomain cleavage, remain to be answered. Apart from these specific questions, a promising new tool has been developed-mice with a global or tissue-specific knockout of FNDC5. In this review, we critically examine the current knowledge and delineate potential solutions to resolve existing ambiguities.

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Published In

Endocr Rev

DOI

EISSN

1945-7189

Publication Date

July 16, 2021

Volume

42

Issue

4

Start / End Page

436 / 456

Location

United States

Related Subject Headings

  • Muscle, Skeletal
  • Mice
  • Humans
  • Fibronectins
  • Endocrinology & Metabolism
  • Biology
  • Animals
  • Adipose Tissue, White
  • Adipose Tissue
  • 3215 Reproductive medicine
 

Citation

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Maak, S., Norheim, F., Drevon, C. A., & Erickson, H. P. (2021). Progress and Challenges in the Biology of FNDC5 and Irisin. Endocr Rev, 42(4), 436–456. https://doi.org/10.1210/endrev/bnab003
Maak, Steffen, Frode Norheim, Christian A. Drevon, and Harold P. Erickson. “Progress and Challenges in the Biology of FNDC5 and Irisin.Endocr Rev 42, no. 4 (July 16, 2021): 436–56. https://doi.org/10.1210/endrev/bnab003.
Maak S, Norheim F, Drevon CA, Erickson HP. Progress and Challenges in the Biology of FNDC5 and Irisin. Endocr Rev. 2021 Jul 16;42(4):436–56.
Maak, Steffen, et al. “Progress and Challenges in the Biology of FNDC5 and Irisin.Endocr Rev, vol. 42, no. 4, July 2021, pp. 436–56. Pubmed, doi:10.1210/endrev/bnab003.
Maak S, Norheim F, Drevon CA, Erickson HP. Progress and Challenges in the Biology of FNDC5 and Irisin. Endocr Rev. 2021 Jul 16;42(4):436–456.
Journal cover image

Published In

Endocr Rev

DOI

EISSN

1945-7189

Publication Date

July 16, 2021

Volume

42

Issue

4

Start / End Page

436 / 456

Location

United States

Related Subject Headings

  • Muscle, Skeletal
  • Mice
  • Humans
  • Fibronectins
  • Endocrinology & Metabolism
  • Biology
  • Animals
  • Adipose Tissue, White
  • Adipose Tissue
  • 3215 Reproductive medicine