Dana-Farber scientists discover hormone that triggers fat to burn energy

Boston scientists have discovered a hormone that is secreted by muscles during exercise and boosts the amount of energy the body burns, a finding that could lay the basis for new drugs for obesity, diabetes, and other diseases. A Boston startup company, Ember Therapeutics, has already licensed the technology and is working to develop a form of the hormone that could be used as a drug that would mimic some of the benefits of exercise.

The new work, published online in the journal Nature, was led by Bruce Spiegelman, a cell biologist at Dana-Farber Cancer Institute and Harvard Medical School. For years, he has been unraveling questions about the formation and nature of “brown fat,” a type of fat that burns energy rather than storing it. Spiegelman and colleagues discovered that the hormone, which they named irisin, triggers changes to ordinary “white” fat that makes them resemble brown fat and increase energy expenditure.

When they induced greater levels of the hormone in obese, pre-diabetic mice over a short period, they saw slight weight loss, increased energy expenediture, and improvements in insulin resistance, a risk factor for diabetes.

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“It’s a hormone made by muscle, put into the blood, and with exercise it increases,” Spiegelman said. “It seems to embody some of what exercise is known to do, which is have an antidiabetes, antiobesity effect.”

Many questions remain, and Spiegelman’s laboratory is already working on many of them. More extensive animal testing of the hormone is underway, to see how big a therapeutic effect can be attained. The laboratory is also focused on questions of how exactly the hormone, named after Iris, a Greek messenger goddess, works to achieve its promising effects: for example, how does the message sent by muscle to fat cells get translated—what is the cellular component, called a receptor, that receives the message?

Meanwhile, Ember Therapeutics, which announced last month that it had raised $34 million from Third Rock Ventures, has put a priority on finding a way to optimize the hormone to create an experimental drug that might help fight various diseases by activating brown fat. Spiegelman is a co-founder of the company, but the present work occurred at his academic laboratory and was funded by the National Institutes of Health.

Brown fat has been known to exist for years, but was thought to be an energy-burning fat found in infants that is lost as we age. But researchers now know that adults have small amounts of brown fat.

“Over the last three years or so, there’s really been an explosion in the work and discoveries in the brown fat area. ... It’s active, it’s activatable,” said Lou Tartaglia, chief executive of Ember Therapeutics. He said obesity treatments that work to increase energy expenditure could be safer than medications that suppress appetite. That’s because such compounds would not have to work on the central nervous system or the brain.

Mitchell Lazar, director of the Institute for Diabetes, Obesity and Metabolism at the University of Pennsylvania, who was not involved in the research, said that the new finding provides an exciting way to attack problems that range from obesity to diabetes, to—possibly—cancer.

“It’s a new molecule and a new pathway and a new mechanism for thinking about how to get at this very, very difficult problem of treating chronic diseases that are affecting tens of millions of people,” Lazar said. But he added that it raises many new questions, from basic ones about what happens if levels of the hormone drops, to understanding better the role it plays in the body.

The new work also underlines an emerging question in the field of brown fat. Why would exercise, which already increases energy expenditure, also cause an increase in the kind of fat that burns energy? Evolutionarily, wouldn’t it make more sense for exercise to increase the storage of energy, for next time?

“From the point of view of how it benefits the person to have this pathway, it’s really not clear at this time, and that will be a very interesting subject for future research that might end up determining whether this will be a novel way to get to the goal we want,” Lazar said.