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Progress and Challenges in the Biology of FNDC5 and Irisin
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 whi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284618/ https://www.ncbi.nlm.nih.gov/pubmed/33493316 http://dx.doi.org/10.1210/endrev/bnab003 |
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author | Maak, Steffen Norheim, Frode Drevon, Christian A Erickson, Harold P |
author_facet | Maak, Steffen Norheim, Frode Drevon, Christian A Erickson, Harold P |
author_sort | Maak, Steffen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8284618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82846182021-07-19 Progress and Challenges in the Biology of FNDC5 and Irisin Maak, Steffen Norheim, Frode Drevon, Christian A Erickson, Harold P Endocr Rev Review 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. Oxford University Press 2021-01-25 /pmc/articles/PMC8284618/ /pubmed/33493316 http://dx.doi.org/10.1210/endrev/bnab003 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Review Maak, Steffen Norheim, Frode Drevon, Christian A Erickson, Harold P Progress and Challenges in the Biology of FNDC5 and Irisin |
title | Progress and Challenges in the Biology of FNDC5 and Irisin |
title_full | Progress and Challenges in the Biology of FNDC5 and Irisin |
title_fullStr | Progress and Challenges in the Biology of FNDC5 and Irisin |
title_full_unstemmed | Progress and Challenges in the Biology of FNDC5 and Irisin |
title_short | Progress and Challenges in the Biology of FNDC5 and Irisin |
title_sort | progress and challenges in the biology of fndc5 and irisin |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284618/ https://www.ncbi.nlm.nih.gov/pubmed/33493316 http://dx.doi.org/10.1210/endrev/bnab003 |
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