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About Sickkids
About SickKids

July 26, 2009

Battling the bulge?

SickKids scientists find the immune system weighs heavily in reducing the health risks of obesity and Type 2 diabetes

TORONTO – We all know your immune system protects you from viruses and bacteria, but what if it could also help protect you from obesity? New research from The Hospital for Sick Children (SickKids), Mount Sinai Hospital, the University of Toronto and Stanford University suggests that the immune system plays a major role in regulating obesity and Type 2 diabetes. The study is published in the July 26 advance online edition of Nature Medicine.

People with Type 2 diabetes are insulin resistant, meaning normal amounts of insulin are not enough. In this study, the researchers have found a way to trigger the immune system into decreasing insulin resistance and blood sugar abnormalities, as well as reducing weight gain.

Obesity has become a widespread global health problem. According to the World Health Organization (WHO), there are nearly one billion overweight adults around the world, with at least 300 million of them categorized as obese, having an abnormal or excessive accumulation of fat that impairs health. Obesity poses a significant risk of developing a wide range of diseases in addition to Type 2 diabetes, including cancer, heart disease and stroke.

“Obesity is a spectrum of disease that gets worse and worse and dieting is less and less efficient as the body fights its host. Until now, we didn’t really understand why some people stay a given weight, others gain weight and some of those who gain end up with full-blown Type 2 diabetes,” says Dr. Hans-Michael Dosch, Principal Investigator of the study, Senior Scientist in Neurosciences & Mental Health at SickKids and Professor in the Departments of Immunology and Paediatrics at the University of Toronto.

In a mouse study of obesity and Type 2 diabetes conducted over the past three years, the research team found that, quite unexpectedly, the immune system plays an important role in the regulation of obesity and is a major controller of blood sugar and insulin function. Insulin is a hormone that provides energy by transporting glucose, or sugar, from the blood into the body’s cells. People with Type 2 diabetes produce a lot of insulin; however, no matter how much they produce, it’s not enough.

The researchers analyzed visceral adipose tissue, which was previously thought to serve as “structural support” for inner organs. They learned that visceral fat is actually a very complex organ: not only does it keep organs in place, it also regulates how efficiently the body uses energy. They found that common immune system cells called T cells are attracted to fat tissue. In obese mice, these T cells actually control insulin resistance, normalize blood sugar and restrict weight gain from overeating. These T cells are antigen-specific, meaning a visceral fat component triggers a specific immune response.

“That was a real shock to us because this says obesity, as it progresses, becomes more and more like an autoimmune disease,” says Dosch. He cites other autimmune diseases such as multiple sclerosis and Type 1 diabetes as typical forms of autoimmunity in which the body fails to recognize its own cells and triggers a damaging immune response against itself. However, by regulating obesity and reducing fat and insulin resistance, this newly-discovered form of autoimmunity is actually good for the body. “Before now, we’ve never had an example of autoimmunity that’s good for you,” he explains.

Over time, the protective function of the fat-associated T cells fails in the face of continued calorie overload. The protective T cell functions decline, overwhelmed by other T cells that promote insulin resistance, so the disease progresses. But still there is good news: to counteract this change, the scientists used an antibody against a T cell membrane component called CD3, which has been available in Canada for about 20 years as an immunosuppressive drug to prevent rejection in both adult and paediatric transplant patients.

Mice were given a short-course (five-day) treatment of anti-CD3 which produced a dramatic reduction in insulin resistance and elevated blood sugar levels, as well as weight loss of about 30 per cent of their body weight. The treatment effects persisted about four to six months in mice. In humans this might translate to several years.

One of the key benefits the scientists found was that even if the weight eventually came back because of the supercaloric diets used, the insulin resistance was kept at bay.

“We now understand why some people don’t progress to Type 2 diabetes – the T cells guard against it. And if the process gets out of hand we can reset it, just as we would reboot a computer,” says Dosch.

Pathologists at Stanford conducted similar histology tests on human fat tissue remaining from surgeries in adult patients. The results of the human experiments closely supported the conclusions drawn from the Toronto mouse experiments.

Using an existing drug could significantly speed up the process of translating the research into full-blown clinical trials in humans who need it. In the clinical trial, researchers will determine the best time and dose to administer the drug to patients for optimal results and will monitor how long the treatment effects last. Clinical trials could begin within 12 months.

Now the ultimate goal, Dosch says, is the development of a vaccine that would protect people from obesity and Type 2 diabetes, a possibility that would make treatments affordable in the third world.

The studies were supported by the Canadian Institutes of Health Research, the Banting & Best Foundation and SickKids Foundation.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

For more information, please contact:

Matet Nebres
The Hospital for Sick Children
Phone: 416-813-6380
email: matet.nebres@sickkids.ca

Suzanne Gold
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
email: suzanne.gold@sickkids.ca