TitleDetection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry.
Publication TypeJournal Article
Year of Publication2015
AuthorsJedrychowski, MP, Wrann, CD, Paulo, JA, Gerber, KK, Szpyt, J, Robinson, MM, K Nair, S, Gygi, SP, Spiegelman, BM
JournalCell Metab
Volume22
Issue4
Pagination734-40
Date Published2015 Oct 06
ISSN1932-7420
KeywordsAdult, Amino Acid Sequence, Body Mass Index, Chromatography, High Pressure Liquid, Electrophoresis, Polyacrylamide Gel, Exercise, Fibronectins, Humans, Isotope Labeling, Male, Molecular Sequence Data, Peptides, Tandem Mass Spectrometry, Young Adult
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.

DOI10.1016/j.cmet.2015.08.001
Alternate JournalCell Metab.
PubMed ID26278051
PubMed Central IDPMC4802359
Grant ListDK90861 / DK / NIDDK NIH HHS / United States
K99 NS087096 / NS / NINDS NIH HHS / United States
NS087096 / NS / NINDS NIH HHS / United States
UL1TR000135 / TR / NCATS NIH HHS / United States
RC4 DK090861 / DK / NIDDK NIH HHS / United States
R01 DK054477 / DK / NIDDK NIH HHS / United States
T32DK007352 / DK / NIDDK NIH HHS / United States
K01 DK098285 / DK / NIDDK NIH HHS / United States
DK31405 / DK / NIDDK NIH HHS / United States
UL1 TR000135 / TR / NCATS NIH HHS / United States
DK098285 / DK / NIDDK NIH HHS / United States
R01AG09531 / AG / NIA NIH HHS / United States
R37 DK031405 / DK / NIDDK NIH HHS / United States
T32 DK007352 / DK / NIDDK NIH HHS / United States
R01 DK031405 / DK / NIDDK NIH HHS / United States
R01 AG009531 / AG / NIA NIH HHS / United States
R01 GM067945 / GM / NIGMS NIH HHS / United States