FNDC5/Irisin Is Not Only a Myokine but Also an Adipokine

Arturo Roca-Rivada,
Cecilia Castelao,
Lucía L. Senin,
María O. Landrove,
Javier Baltar,
Ana Belén Crujeiras,
Luisa María Seoane,
Felipe F. Casanueva,
María Pardo mail

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Abstract

Exercise provides clear beneficial effects for the prevention of numerous diseases. However, many of the molecular events responsible for the curative and protective role of exercise remain elusive. The recent discovery of FNDC5/irisin protein that is liberated by muscle tissue in response to exercise might be an important finding with regard to this unsolved mechanism. The most striking aspect of this myokine is its alleged capacity to drive brown-fat development of white fat and thermogenesis. However, the nature and secretion form of this new protein is controversial. The present study reveals that rat skeletal muscle secretes a 25 kDa form of FNDC5, while the 12 kDa/irisin theoretical peptide was not detected. More importantly, this study is the first to reveal that white adipose tissue (WAT) also secretes FNDC5; hence, it may also behave as an adipokine. Our data using rat adipose tissue explants secretomes proves that visceral adipose tissue (VAT), and especially subcutaneous adipose tissue (SAT), express and secrete FNDC5. We also show that short-term periods of endurance exercise training induced FNDC5 secretion by SAT and VAT. Moreover, we observed that WAT significantly reduced FNDC5 secretion in fasting animals. Interestingly, WAT of obese animals over-secreted this hormone, which might suggest a type of resistance. Because 72% of circulating FNDC5/irisin was previously attributed to muscle secretion, our findings suggest a muscle-adipose tissue crosstalk through a regulatory feedback mechanism.

Citation: Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, et al. (2013) FNDC5/Irisin Is Not Only a Myokine but Also an Adipokine. PLoS ONE 8(4): e60563. doi:10.1371/journal.pone.0060563
Editor: Raul M. Luque, University of Cordoba, Spain
Received: November 2, 2012; Accepted: February 28, 2013; Published: April 11, 2013
Copyright: © 2013 Roca-Rivada et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work has been funded by Instituto de Salud Carlos III (Ministerio de Economía y Competitividad de España): FISP10/00537. AR-R and CC are funded by CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III. MP is a Miguel Servet Fellow (Instituto de Salud Carlos III/SERGAS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.