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Reaping benefits of exercise minus the sweat.

Article / Review by on January 11, 2012 – 8:33 pmNo Comments

Reaping benefits of exercise minus the sweat.
Researchers isolate messenger protein linking exercise to health benefits

"There has been a feeling in the field that exercise ‘talks to’ various tissues in the body," said Bruce Spiegelman (right), a professor of cell biology at Harvard Medical School. "But the question has been, how?"/ File photo by Justin Ide/Harvard Staff Photographer“There has been a feeling in the field that exercise ‘talks to’ various tissues in the body,” said Bruce Spiegelman (right), a professor of cell biology at Harvard Medical School. “But the question has been, how?”/ File photo by Justin Ide/Harvard Staff Photographer

A team led by researchers at Harvard-affiliated Dana-Farber Cancer Institute has isolated a natural hormone from muscle cells that triggers some of the key health benefits of exercise. They say the protein, which serves as a chemical messenger, is a highly promising candidate for development as a novel treatment for diabetes, obesity, and perhaps other disorders, including cancer.

Bruce Spiegelman, a cell biologist at Dana-Farber, is senior author of the report, posted as an advance online publication by the journal Nature. The first author is Pontus Bostrom, a postdoctoral fellow in the Spiegelman lab.

“It’s exciting to find a natural substance connected to exercise that has such clear therapeutic potential,” said Bostrom.

Spiegelman dubbed the hormone “irisin,” after Iris, a Greek messenger goddess. He said the discovery is 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.

“There has been a feeling in the field that exercise ‘talks to’ various tissues in the body,” said Spiegelman, a professor of cell biology at Harvard Medical School. “But the question has been, how?”

According to the report, the irisin hormone has direct and “powerful effects” on adipose, or fatty, tissue — subcutaneous deposits of white fat that store excess calories and that contribute to obesity.

When irisin levels rise through exercise — or, in this study, when irisin was injected into mice — the hormone switches on genes that convert white fat into “good” brown fat. This is beneficial because brown fat burns off more excess calories than does exercise alone.

Only a small amount of brown fat is found in adults, but infants have more — an evolutionary echo of how mammals keep themselves warm while hibernating. In the wake of findings by Spiegelman and others, there has been a surge of interest in the therapeutic possibilities of increasing brown fat in adults.

Along with stimulating brown fat development, irisin was shown to improve glucose tolerance, a key measure of metabolic health, in mice fed a high-fat diet.

The discovery won’t allow people to skip the gym and build muscles by taking irisin supplements, Spiegelman cautioned, because the hormone doesn’t appear to make muscles stronger. Experiments showed that irisin levels increase as a result of repeated bouts of prolonged exercise, but not during short-term muscle activity.

The Dana-Farber team identified irisin in a search for genes and proteins regulated by a master metabolic regulator, called PGC1-alpha, which is turned on by exercise. Spiegelman’s group had discovered PGC1-alpha in previous research.

Bostrom said the hunt for molecular targets of increased PGC1-alpha activity ultimately pinpointed irisin, which turned out to be located within the outer membrane of muscle cells. This discovery ran counter to other scientists’ contentions that such a protein would reside in the cell’s nucleus.

To test whether increasing irisin alone could mimic exercise benefits, the scientists injected modest amounts into sedentary mice that were obese and pre-diabetic.

With 10 days of treatment, the mice had better control of blood sugar and insulin levels — in effect, preventing the onset of diabetes — and lost a small amount of weight. Although the weight loss was small, Spiegelman said that the hormone may have a greater effect when given for longer periods.

There were no signs of toxicity or side effects, a finding that was predicted because the researchers limited the increase of irisin to levels typically caused by exercise.

In part because it is a natural substance and because the mouse and human forms of the protein are identical, Spiegelman said it should be possible to move an irisin-based drug rapidly into clinical testing — perhaps within two years.

The irisin discovery has been licensed by Dana-Farber exclusively to Ember Therapeutics for drug development. Ember is a Boston-based startup co-founded by Spiegelman and scientists at the Harvard-affiliated Joslin Diabetes Center and the Scripps Research Institute in Florida.

The scientists said their findings merely scratch the surface of irisin’s multiple effects. They are continuing to explore the hormone’s possible benefits in metabolic diseases like diabetes, insulin resistance, and obesity, which constitute a growing epidemic around the world, as well as neurodegenerative illnesses such as Parkinson’s disease.

Spiegelman added that as growing evidence implicates obesity and physical inactivity in cancer development, it’s conceivable irisin-based drugs may have value in prevention and treatment of the disease.

Other authors, in addition to Spiegelman and Bostrom, are from Dana-Farber; Harvard Medical School; Harvard affiliated Brigham and Women’s Hospital; University of California, San Francisco; Universita Politecnica delle Marche, Ancona, Italy; Odense University Hospital, Denmark; andLakePharma, Belmont, Calif.

The National Institutes of Health funded the research.

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Harvard School of Public Health is dedicated to advancing the public’s health through learning, discovery and communication. More than 400 faculty members are engaged in teaching and training the 1,000-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children’s health to quality of care measurement; from health care management to international health and human rights.

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Established in 1636, Harvard is the oldest institution of higher education in the United States. The University, which is based in Cambridge and Boston, Massachusetts, has an enrollment of over 20,000 degree candidates, including undergraduate, graduate, and professional students. Harvard has more than 360,000 alumni around the world.

Harvard University is devoted to excellence in teaching, learning, and research, and to developing leaders in many disciplines who make a difference globally. Harvard faculty are engaged with teaching and research to push the boundaries of human knowledge. For students who are excited to investigate the biggest issues of the 21st century, Harvard offers an unparalleled student experience and a generous financial aid program, with over $160 million awarded to more than 60% of our undergraduate students. The University has twelve degree-granting Schools in addition to the Radcliffe Institute for Advanced Study, offering a truly global education.

‘Universities nurture the hopes of the world: in solving challenges that cross borders; in unlocking and harnessing new knowledge; in building cultural and political understanding; and in modeling environments that promote dialogue and debate… The ideal and breadth of liberal education that embraces the humanities and arts as well as the social and natural sciences is at the core of Harvard’s philosophy. ’/ Drew Gilpin Faust

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*  The above story is adapted from materials provided by Harvard University

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