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Evidence against a Beneficial Effect of Irisin in Humans

Raschke, Silja; Elsen, Manuela; Gassenhuber, Hans; Sommerfeld, Mark; Schwahn, Uwe; Brockmann, Barbara; Jung, Raphael; Wisløff, Ulrik; Tjønna, Arnt Erik; Raastad, Truls; Hallén, Jostein; Norheim, Frode; Drevon, Christian A; Romacho, Tania; Eckardt, Kristin; Eckel, Juergen
Journal article, Peer reviewed
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http://hdl.handle.net/11250/2360568
Utgivelsesdato
2013
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  • Publikasjoner fra CRIStin - NTNU [26591]
Originalversjon
PLoS ONE 2013, 8(9)   10.1371/journal.pone.0073680
Sammendrag
Brown adipose tissue has gained interest as a potential target to treat obesity and metabolic diseases. Irisin is a newly

identified hormone secreted from skeletal muscle enhancing browning of white fat cells, which improves systemic

metabolism by increasing energy expenditure in mice. The discovery of irisin raised expectations of its therapeutic potential

to treat metabolic diseases. However, the effect of irisin in humans is unclear. Analyses of genomic DNA, mRNA and

expressed sequence tags revealed that FNDC5, the gene encoding the precursor of irisin, is present in rodents and most

primates, but shows in humans a mutation in the conserved start codon ATG to ATA. HEK293 cells transfected with a human

FNDC5 construct with ATA as start codon resulted in only 1% full-length protein compared to human FNDC5 with ATG.

Additionally, in vitro contraction of primary human myotubes by electrical pulse stimulation induced a significant increase

in PGC1a mRNA expression. However, FNDC5 mRNA level was not altered. FNDC5 mRNA expression in muscle biopsies from

two different human exercise studies was not changed by endurance or strength training. Preadipocytes isolated from

human subcutaneous adipose tissue exhibited differentiation to brite human adipocytes when incubated with bone

morphogenetic protein (BMP) 7, but neither recombinant FNDC5 nor irisin were effective. In conclusion, our findings

suggest that it is rather unlikely that the beneficial effect of irisin observed in mice can be translated to humans.
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Public Library of Science
Tidsskrift
PLoS ONE

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