Detection and quantitation of circulating human irisin by tandem mass spectrometry

Mark P. Jedrychowski, Christiane D. Wrann, Joao A. Paulo, Kaitlyn K. Gerber, John Szpyt, Matthew M. Robinson, K Sreekumaran Nair, Steven P. Gygi, Bruce M. Spiegelman

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

Exercise provides many health benefits, including improved metabolism, cardiovascular health, and cognition. We have shown previously that FNDC5, a type I transmembrane protein, and its circulating form, irisin, convey some of these benefits in mice. However, recent reports questioned the existence of circulating human irisin both because human FNDC5 has a non-canonical ATA translation start and because of claims that many human irisin antibodies used in commercial ELISA kits lack required specificity. In this paper we have identified and quantitated human irisin in plasma using mass spectrometry with control peptides enriched with heavy stable isotopes as internal standards. This precise state-of-the-art method shows that human irisin is mainly translated from its non-canonical start codon and circulates at ∼3.6 ng/ml in sedentary individuals; this level is increased to ∼4.3 ng/ml in individuals undergoing aerobic interval training. These data unequivocally demonstrate that human irisin exists, circulates, and is regulated by exercise.

Original languageEnglish (US)
Pages (from-to)734-740
Number of pages7
JournalCell Metabolism
Volume22
Issue number4
DOIs
StatePublished - Oct 6 2015

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Tandem Mass Spectrometry
Initiator Codon
Insurance Benefits
Isotopes
Cognition
Mass Spectrometry
Enzyme-Linked Immunosorbent Assay
human FNDC5 protein
Peptides
Antibodies
Health
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Jedrychowski, M. P., Wrann, C. D., Paulo, J. A., Gerber, K. K., Szpyt, J., Robinson, M. M., ... Spiegelman, B. M. (2015). Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metabolism, 22(4), 734-740. https://doi.org/10.1016/j.cmet.2015.08.001

Detection and quantitation of circulating human irisin by tandem mass spectrometry. / Jedrychowski, Mark P.; Wrann, Christiane D.; Paulo, Joao A.; Gerber, Kaitlyn K.; Szpyt, John; Robinson, Matthew M.; Nair, K Sreekumaran; Gygi, Steven P.; Spiegelman, Bruce M.

In: Cell Metabolism, Vol. 22, No. 4, 06.10.2015, p. 734-740.

Research output: Contribution to journalArticle

Jedrychowski, MP, Wrann, CD, Paulo, JA, Gerber, KK, Szpyt, J, Robinson, MM, Nair, KS, Gygi, SP & Spiegelman, BM 2015, 'Detection and quantitation of circulating human irisin by tandem mass spectrometry', Cell Metabolism, vol. 22, no. 4, pp. 734-740. https://doi.org/10.1016/j.cmet.2015.08.001
Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metabolism. 2015 Oct 6;22(4):734-740. https://doi.org/10.1016/j.cmet.2015.08.001
Jedrychowski, Mark P. ; Wrann, Christiane D. ; Paulo, Joao A. ; Gerber, Kaitlyn K. ; Szpyt, John ; Robinson, Matthew M. ; Nair, K Sreekumaran ; Gygi, Steven P. ; Spiegelman, Bruce M. / Detection and quantitation of circulating human irisin by tandem mass spectrometry. In: Cell Metabolism. 2015 ; Vol. 22, No. 4. pp. 734-740.
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