Lucky Mice: Researchers Have Found a Protein that Mimics the Effects of Exercise

A newly discovered protein could help both mouse and man gain all the benefits of exercise without breaking a sweat

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If you’re like most people, every time you step on the treadmill or sweat your way through a kickboxing class, you’re wondering — when will they develop a pill for this?

It turns out they have. Scientists at the Dana-Farber Cancer Institute and Harvard Medical School have uncovered a key protein in muscle that leads to all the healthy benefits of exercise, which means it can improve blood sugar levels and melt away pounds without so much as an ounce of effort.

The problem is, the work is limited to mice.

The compound is a membrane protein in muscle cells — found both in humans and in mice — that’s broken down during exercise and secreted as a hormone. The researchers call this newly identified hormone “irisin,” named after Iris, the messenger of the gods in Greek mythology.

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Irisin acts as a chemical messenger in the body, with a “profound” impact on fat cells, according to the Boston scientists. Writing this week in the journal Nature, they say that irisin induces ordinary “white” fat cells to convert into “brown fat,” a type of adipose tissue that helps to regulate body temperature, while burning a tremendous amount of energy in the process. In people, brown fat stores are greatest in newborns, who need the extra heat generated by the burning fat cells to keep their body temperatures close to that found in their mother’s womb, at least until they acclimate to our rather chillier world. Adults have only small stores of brown fat, mostly in the back of the neck, and for years, scientists have been eager to find ways to activate or enhance this stingy deposit. The reason? In both humans and mice, as brown-fat stores increase and white-fat stores shrink following exercise, we experience “a significant increase in total body energy expenditure,” the researchers write.

Further experiments in mice suggest that the metabolic shift can improve the body’s ability to break down glucose — and lower the risk of diabetes — while promoting weight loss. In typically understated science-speak, the researchers go on to say that, “The therapeutic potential of irisin is obvious.”

On Wednesday, Dana-Farber Cancer Institute announced that it had licensed irisin for pharmaceutical development to Ember Therapeutics. Ember is a Boston-based start-up, co-founded by Bruce Spiegelman, who runs the laboratory that isolated irisin.

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Spiegelman and his colleagues followed a fascinating path to uncover the role of their newfound hormone. They began with a molecular hunt, searching for genes and proteins that might be regulated by a substance known as PGC1-alpha, which mediates many effects of exercise in muscle. Once they had identified the hormone irisin, they then tested it and found that it could induce “browning” of fat cells both in cultured cells and in live mice.

Following that, they confirmed that in both mice and adult humans, blood levels of irisin rose following participation in a monitored exercise regime. Adults who followed a ten-week endurance program doubled their blood irisin levels, on average, over the two and a half months of the exercise regimen.

Finally, Spiegelman and colleagues showed that irisin could ease existing health problems among mice that had been rendered obese and diabetic through a high-fat diet. The researchers injected the mice with irisin. On average, after 10 days, the mice had lost weight (just a little, though), showed considerably improved glucose tolerance, and were better able to ward off diabetes. Similar mice not given irisin showed no such changes. It’s those findings that best hint at the therapeutic possibilities of irisin — exercise in a pill.

One final mystery remains, however: Why would exercise promote the formation of brown fat? Brown fat helps the body with heat regulation, but it burns a lot of extra calories in the process — and for most of human history we probably haven’t had many extra calories to spare.

In their Nature paper, the researchers write:

[I]t seems paradoxical that exercise would stimulate the secretion of a polypeptide hormone that increases [...] energy expenditure. One explanation for increased irisin expression with exercise in mouse and man may be that it evolved as a consequence of muscle contraction during shivering. Muscle secretion of a hormone that activates adipose thermogenesis during this process might provide a broader, more robust defence against hypothermia.

In extremely cold weather, that is, muscles work hard through shivering. In turn, shivering may send messages to the body to create more brown fat that will better regulate heat.

As exciting as the potential of irisin is, Spiegelman stresses that there is still a lot more we need to understand about brown fat metabolism before the compound can be tested in people. That means that for now, the findings don’t change existing health advice about the benefits of eating a nutritious diet and getting regular exercise. Even if irisin were to become available, can’t mimic all the health benefits of exercise. It can’t build muscle and strengthen bones, for example.

“We’re not trying to replace diet and exercise,” Spiegelman told Bloomberg News. “That’s still important.”

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