Washington: Researchers have confirmed the existence of irisin, a hormone linked to the positive benefits of exercise. Irisin’s discovery in 2012 was exciting because scientists had potentially found a reason why exercise keeps us healthy. However, the existence of irisin in humans was recently questioned. Two studies pointed to possible flaws in the methods used to identify irisin, with commercially available antibodies. Scientists who discovered irisin addressed this contentious issue by showing that human irisin circulates in the blood at nanogram levels and increases during exercise.
Senior author Bruce Spiegelman of Dana-Farber Cancer Institute and Harvard Medical School said that the confusion over irisin comes down to disagreement over how irisin protein is made in skeletal muscle cells and the detection limits of protocols. He and co-author Steven Gygi turned to state-of-the-art quantitative mass spectrometry techniques to show that the human hormone uses a rare signal ATA (start codon) to initiate its production (translation) rather than the usual ATG. The use of the ATA, rather than the more common ATG, had led some researchers to conclude that the human gene was a pseudogene – a gene that serves no function.
But alternative start codons account for a few of all genes and are usually an indication of complex regulation. The researchers showed that human irisin is similar to the mouse hormone and it circulates in the range previously reported. Although irisin circulates at low levels (nanograms), this range is comparable to that observed for other important biological hormones such as insulin. Furthermore, the researchers developed a protocol, that does not rely on antibodies, to precisely measure how much irisin increases in people after exercise. “The data are compelling and clearly demonstrate the existence of irisin in circulation,” said endocrinologist Francesco Celi of the Virginia Commonwealth University Medical Centre, who was not involved with the study.
“Importantly, the authors provide a precise and reproducible protocol to measure irisin,” Celi said. The authors point out one caveat in their methods – that some irisin is lost during sample preparation, and therefore the amount of irisin detected is a slight underestimation. The technology is also expensive and requires specific mass spectrometry instruments. However, future refinement of this work should lead to more scalable protocols, the researchers said. “Spiegelman and colleagues have unequivocally shown that the ‘mythical’ irisin peptide is produced as a result of exercise,” said chemical physiologist John Yates of The Scripps Research Institute, also not affiliated with the work. “This data should settle the controversy surrounding the existence of irisin and its increase in blood as a function of exercise,” Yates said. The study was published in the journal Cell Metabolism.
