Researchers from the Hospital for Sick Children, along with their colleagues from the University of Toronto, Mount Sinai Hospital and Stanford University in California, collaborated on a revolutionary study in which a new immune defense system against weight gain has been discovered. The scientists found that the immune system actually targets its own fat, but that this defense is overwhelmed by chronic overeating and it loses its ability to keep fat under control. To their surprise, however, they found that the immune system can be “rebooted” by a readily available drug, potentially offering a less invasive alternative to bariatric surgery in the future. The approved drug, known as anti-CD3, has been used for the past 20 years to combat organ rejection in transplants. It is able to reset the normal fat-fighting balance of the immune system. The research also points to a reason that obesity can lead to Type 2 diabetes, one of many autoimmune diseases that occur when the immune system turns against a working part of the body and cripples its function.

Dr. Hans-Michael Dosch, the paper's senior author, says that the research is the first to demonstrate that an “autoimmune response” can be beneficial to one's health. In the case of fat, he explains, nature provides T cells that specifically target that tissue, like it were a germ or a virus, when it starts to grow inside the abdominal cavity. “These good T cells, known as TH2, sit amid the body's visceral fat and are activated when we begin to gain weight there,” says Dr. Dosch. "There is no other example for good autoimmunity that we are aware of," he adds, noting that “the beneficial immune process explains earlier research that showed a plethora of dead fat cells could typically be found in the blood of people who were gaining weight.”

So why is obesity linked to Type 2 diabetes? According to Dr. Dosch, fat cells get fatter because they naturally gorge on as much blood glucose as possible, and “a new and dangerous set of immune agents becomes more active, turning that growing store of fat into the equivalent of a festering wound.” These inflammatory T cells are much like those that cause swelling around an open wound. “They proliferate inside the fat cells, turning the entire mass into a big sore spot,” he says. “It's been known if you have a serious tissue wound anywhere, you actually become insulin-resistant," he says. In the studies using mice, a short course of anti-CD3 produced a 30 percent drop in body weight and a dramatic reversal of insulin resistance.

Although the research was conducted on mice, Dr. Philip Sherman, scientific director of nutrition, metabolism and diabetes with the Canadian Institutes of Health Research, which helped fund the study, says it may have relevance for humans. “It is an important paper -- an important, fundamental advance. It's a novel way of thinking about managing diabetes," he says.

News Release: Immune system may help fight obesity  www.thestar.com    July 27, 2009