The “Exercise Hormone” Irisin Is NOT a Myth

Researchers who discovered irisin confirm that irisin increases during exercise.

Posted Aug 14, 2015

 I T A L O/Shutterstock
Source: I T A L O/Shutterstock

Irisin, a hormone also known as FNDC5, has been linked to many of the positive benefits associated with physical exercise. In the past year, a controversy erupted over possible flaws in the methods that the scientists who discovered the benefits of irisin had used during their research. 

In the August 2015 issue of Cell Metabolism the Harvard scientists who discovered irisin—Bruce SpiegelmanSteven Gygi and colleagues—address this contentious issue by proving that human irisin does in fact circulate in the blood at nanogram levels and increases during exercise.

The new 2015 study, "Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry," confirms the existence of exercise-induced irisin and its potential health benefits. The authors state, "These data unequivocally demonstrate that human irisin exists, circulates, and is regulated by exercise."

According to Bruce Spiegelman, PhD, a cell biologist and senior study author of Dana-Farber Cancer Institute and Harvard Medical School, the recent confusion over irisin is based on a disagreement over how irisin protein is made in skeletal muscle cells and the detection limits of protocols.

In 2012, Spiegelman dubbed the hormone FNDC5 "irisin," after Iris, a Greek messenger goddess. Irisin's discovery created excitment because scientists had potentially found a key reason that exercise keeps us healthy. Research on mice showed that when irisin levels were increased, blood and metabolism improved.

Spiegelman foresaw the role of irisin as a ‘messenger’ saying, "There has been a feeling in the field that exercise 'talks to' various tissues in the body. But the question has been, how?" His ongoing research—along with that of others around the globe—continues to help solve the irisin riddle.

In a 2014 Psychology Today blog post, "Irisin: The 'Exercise Hormone' has Powerful Health Benefits," I wrote,

If you need one more reason to motivate yourself to be more physically active, you can add the exercise induced hormone irisin to your list. In the past two years scientists have discovered that a hormone called irisin—which is released after moderate endurance aerobic activity—has the ability to help maintain healthy body weight, improve cognition, and slow the aging process.

Wikimedia/Creative Commons

The "Exercise Hormone" Irisin (FNDC5)

Source: Wikimedia/Creative Commons

At the time of irisin's initial discovery, Spiegelman believed that it was an important first step in understanding the biological mechanisms that translate physical exercise into beneficial changes throughout the body—both in healthy people and in preventing or treating disease. A variety of studies released since 2012 have continued to show that the “exercise hormone” irisin has a wide range of health benefits.

However, a March 2015 study, “Irisin – A Myth Rather Than an Exercise-Inducible Myokin,” argued that the irisin levels reported by commercial kits were actually due to unknown blood proteins and misconstrued the role of the hormone in human metabolism.

To counter claims that exercise-induced irisin was a myth, Spiegelman and co-author Steven Gygi recently used 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 authors explain that the use of the ATA, rather than the more common ATG, had led some investigators 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.

In the latest August 2015 report, Speigelman et al show that human irisin is similar to the mouse hormone and that it circulates in the range previously reported. In a press release the authors state, "Although irisin circulates at low levels (nanograms), this range is comparable to that observed for other important biological hormones such as insulin. Furthermore, the investigators developed a protocol, that does not rely on antibodies, to precisely measure how much irisin increases in people after exercise."

Conclusion: Other Researchers Weigh-In on the "Irisin Is NOT a Myth" Debate

In the press release, John Yates who is a chemical physiologist of The Scripps Research Institute, and was not affiliated with the recent research stated, "Spiegelman and colleagues have unequivocally shown that the "mythical" irisin peptide is produced as a result of exercise. This data should settle the controversy surrounding the existence of irisin and its increase in blood as a function of exercise."

Francesco Celi, an endocrinologist of the Virginia Commonwealth University Medical Center, who was also not involved with the study added, "The data are compelling and clearly demonstrate the existence of irisin in circulation. Importantly, the authors provide a precise and reproducible protocol to measure irisin." 

If you'd like to read more on this topic, check out my Psychology Today blog posts:

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