Characterization of the metabolic effects of irisin on skeletal muscle in vitro.
OBJECTIVE
This work explored the effects of irisin on metabolism, gene expression and mitochondrial content in cultured myocytes.


METHODS
C2C12 myocytes were treated with various concentrations of irisin for various durations. Glycolysis and oxidative metabolism were quantified by measurement of extracellular acidification and oxygen consumption, respectively. Metabolic gene expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and mitochondrial content was assessed by flow cytometry and confocal microscopy.


RESULTS
Cells treated with irisin exhibited significantly increased oxidative metabolism. Irisin treatment also significantly increased mitochondrial uncoupling at various doses and durations. Lastly, treatment with irisin also significantly elevated metabolic gene expression including peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), irisin, glucose transporter 4 (GLUT4) and mitochondrial uncoupling protein 3 (UCP3) leading to increased mitochondrial biogenesis.


CONCLUSIONS
Our observations are the first to document increased metabolism in myocytes through irisin-mediated induction of mitochondrial biogenesis and uncoupling with corresponding gene expression. These observations support the need for further investigation into the therapeutic and pharmacological effects of irisin, as well as development of irisin-based therapy.
Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM, USA; Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Individual, Family, and Community Education: Nutrition, University of New Mexico, Albuquerque, NM, USA.
R A
RA
Vaughan
N P
NP
Gannon
M A
MA
Barberena
R
R
Garcia-Smith
M
M
Bisoffi
C M
CM
Mermier
C A
CA
Conn
K A
KA
Trujillo
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000819:agonists / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects*; D006609:High Mobility Group Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009124:Muscle Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C577593:FNDC5 protein, human; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D006609:High Mobility Group Proteins; D009124:Muscle Proteins; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011994:Recombinant Proteins; C081930:Tfam protein, mouse; D014157:Transcription Factors
fibronectin type III domain containing protein 5 (FNDC5); mitochondrial uncoupling protein 3 (UCP3); myokine; peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)