An international team of scientists has isolated a natural hormone or chemical messenger in muscle cells that triggers some of the important health benefits of exercise. They have named it “irisin”, after the Greek messenger goddess, and believe it is a promising candidate for developing drugs to treat diabetes, obesity and maybe even cancer.
Senior author Dr Bruce Spiegelman, from the Dana-Farber Cancer Institute, in Boston, Massachusetts, and colleagues, write about their findings in the 11 January online issue of Nature. Spiegelman is also professor of cell biology at Harvard Medical School in Boston.
Spiegelman said for a while researchers have had a notion that exercise “talks to various tissues in the body”, but the question was “How?”
First author Dr Pontus Bostrom, a postdoctoral fellow who works with Spiegelman in his lab, told the press:
“It’s exciting to find a natural substance connected to exercise that has such clear therapeutic potential.”
He and his co-authors believe finding irisin is the start of understanding how physical exercise benefits the body biologically, not only to keep people healthy but also to prevent and treat disease.
They came across irisin when they were looking at the effect of exercise on a master metabolic regulator gene called PGC1-alpha, which Spiegelman’s group had already identified in previous work. When exercise switches on this gene, it in turn regulates a cluster of genes and proteins.
A search for these other genes and proteins turned up irisin. They found it in the outer membranes of muscle cells, and not in the nucleus, as other scientists had predicted.
For this study, the researchers used lab cultures and mice to show that irisin has a direct and powerful effect on white adipose tissue, the subcutaneous deposits of white fat that store excess calories and contribute to obesity.
When humans and mice exercise, levels of irisin in the muscles go up, and this switches on a gene that triggers conversion of white fat into “good” brown fat.
A similar thing happened when the researchers injected modest amounts of irisin into sedentary mice that were obese and pre-diabetic It mimicked the effect of exercise, except that their energy expenditure went up “with no changes in movement or food intake”.
Brown fat is called “good” fat because it burns off more excess calories than exercise alone. Since researchers like Spiegelman discovered this, there has been a surge of interest in it.
Adult humans don’t carry much brown fat, while babies have a lot more, possibly a hangover from when our evolutionary ancestors used to hibernate, like many mammals descended from those ancestors do today.
As well as triggering the conversion of white fat into brown fat, the researchers showed that irisin improved glucose tolerance in mice kept on a high-fat diet. Improved glucose tolerance is a key indicator of metabolic health, and the better a person’s metabolic health, the lower their risk of developing cardiovascular diseases and diabetes.
The mice developed this improved glucose tolerance with just 10 days of treatment, and they also lost a small amount of weight. Spiegelman thinks the effect could have been greater if the treatment had lasted longer.
He and his colleagues conclude:
“Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.”
However, Spiegelman warns that this doesn’t mean people will be able to forego the gym and build muscle by taking irisin supplements. The hormone doesn’t seem to work like that: it might stimulate conversion of white fat into brown fat, and increase “thermogenesis” (burn off calories), but it doesn’t make muscles stronger.
Because irisin is a natural substance and the mouse and human forms are the same, Spiegelman reckons clinical testing of a drug based on the protein could be happening in the next two years.
As they predicted, since they kept the irisin doses to within levels that would typically occur with exercise, the researchers said they observed no toxic or side effects.
The discovery has already been licensed for drug development to Ember Therapeutics, a company co-founded by Spiegelman.
Meanwhile, the team is exploring the hormone’s other potential benefits, not only in treating diabetes, insulin resistance, and obesity, but also neurodegenerative diseases like Parkinson’s.
Spiegelman says drugs based on irisin may have potential to prevent and treat cancer as well, especially in the light of growing evidence that lack of physical activity and obesity contributes to its development.
Written by Catharine Paddock PhD