Evidence against a beneficial effect of irisin in humans

• Published in: PloS one 2013-09, Vol.8 (9), p.e73680-e73680
• Main Authors: Raschke, Silja, Elsen, Manuela, Gassenhuber, Hans, Sommerfeld, Mark, Schwahn, Uwe, Brockmann, Barbara, Jung, Raphael, Wisløff, Ulrik, Tjønna, Arnt E, Raastad, Truls, Hallén, Jostein, Norheim, Frode, Drevon, Christian A, Romacho, Tania, Eckardt, Kristin, Eckel, Juergen
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipose tissue; Adipose tissue (brown); Adolescent; Adult; Amino Acid Sequence; Animals; Base Sequence; Bone morphogenetic proteins; Browning; Cells, Cultured; Codon, Initiator - genetics; Codons; Contraction; Deoxyribonucleic acid; Diabetes; DNA; Endurance; Energy; Energy expenditure; Energy metabolism; Exercise; Expressed sequence tags; Female; Fibronectins - genetics; Fibronectins - metabolism; Gene expression; Gene Expression Profiling; Genes; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Health aspects; HEK293 Cells; Humans; Male; Medical imaging; Medicine; Messenger RNA; Metabolic disorders; Metabolism; Mice; Microscopy, Fluorescence; Middle Aged; Molecular Sequence Data; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Mutation; Myotubes; Nucleotide sequence; Nutrition; Obesity; Physiological aspects; Physiology; Preadipocytes; Primates; Protection and preservation; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Skeletal muscle; Type 2 diabetes; Weight training; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073680

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 PGC1α 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.