Finally, researchers link inflammation to illness in overweight people...

Researchers are beginning to understand the ways in which being overweight or obese contributes to a downward spiral of inflammation that can trigger heart disease, diabetes and other ailments.


Two recent papers help explain the connection. In one, published in the Journal of Clinical Investigation, researchers at the University of California-San Francisco and the Gladstone Institute found that specialized white blood cells exposed to large amounts of saturated fats became inflamed. When the researchers genetically engineered cells to be able to hold more fat, the inflammation didn't happen.

Another, from the Albert Einstein College of Medicine, shows the hormonal cascade caused by fat can contribute to heart disease by producing a protein that keeps blood clots from breaking down.

Those are just two of dozens of labs homing in on how fat can trigger diabetes, heart disease and more.

A new view of fat

Up until about 10 or 15 years ago, doctors thought of fat as just fat, a bunch of cells that stored energy.

That changed in 1994, when researchers at Rockefeller University in New York discovered that fat cells actually produce leptin, a hormone that controls hunger and fat burning.

Suddenly, fat went from being an inert bunch of grease to an important player in the endocrine system. It's now known that fat produces at least 20 proteins, many of them hormones.

Then in 2005, a group at Columbia University in New York showed that when rodents were fed a high fat diet or became obese, their fat tissues became inflamed. This launched a new effort to find the cause.

Normally, inflammation is healthy, a part of the body's fight against infections. But when it happens in response to obesity, it can contribute to numerous ills, such as fatty liver disease, type 2 diabetes and atherosclerosis, says Anthony Ferrante, a medical professor at Columbia whose research focuses on obesity's affects.

The inflammation appears to happen because macrophages, white blood cells that attack and eat infection, congregate in fat tissue.

Why is a mystery. "Are the fat cells getting big, bursting and then the macrophages are going in to clean up the mess? Or is it that the macrophages are killing the fat cells?" asks Carey Lumeng, a pediatrician who studies obesity and inflammation at the University of Michigan-Ann Arbor.

A few years ago, Ferrante's lab discovered that in lean people, only 5% of fat tissue is made up of macrophages, while in the severely obese it can be more than 50%.

And why do they cause an immune response? One hypothesis is that higher concentrations of fat could trigger macrophages to go into inflammatory mode.

Once there, the macrophages recruit "legions of their comrades into the tissue with the idea of setting up a focus of inflammation, as would be the case if there was some sort of infection," says Suneil Koliwad, a researcher at the Gladstone on the Journal of Clinical Investigation paper.

But unlike an infection, "where one either recovers or dies, there is no end to the insult that triggers the inflammatory response. The obese person remains obese and the insult and inflammatory trigger lingers on and on chronically," he says.

Here, inflammation doesn?t mean just swelling. It?s a complex set of biological responses in the tissue during which macrophages cluster and go to work wielding their chemical weapons.

When that happens, they shift from being simple eaters of dead cells to killers of foreign invaders. To do that killing, they bring out chemical weaponry, including cytokines. These are substances that carry signals between cells and can be used to attack and destroy infections.

Research into the cause

The hope is that current research might lead to ways to decrease the body's inflammatory response to the presence of too much fat. The researchers at Albert Einstein took healthy, overweight people and raised their free fatty acid levels. In response, the macrophages started to produce more of a protein that keeps clots from breaking down, says Preeti Kishore, an endocrinologist and author of the report in Science Translational Medicine.

This is bad news for anyone who has heart disease or who's had a heart attack. There you want the clots to break up — fast — so blood flow to the heart isn't limited. But in the obese, too much of the protein kept the clots in place.

In San Francisco, researchers did some nifty genetic engineering to see if the problem was the fat itself. They created macrophages that could simply store more fat, introducing them through bone marrow transplants.

This protected obese mice against the fat-induced inflammatory response, says Koliwad.He calls the research exciting because it gives them "the potential for a therapeutic target to examine" when it comes to the ravages of obesity-induced immune response.

The hope is that current research might lead to ways to decrease the body?s inflammatory response to the presence of too much fat.

Lumeng, a pediatrician, says that's especially important because of the high levels of obesity among American children. Recent research has shown that children as young as three-years-old have the same kind of inflammation markers that adults with heart disease have. Doctors "are very worried about this," and what these long-term obesity and inflammation will mean for the health of America's children as they age. With over a third of children overweight according to the Centers for Disease Control and Prevention, "we're talking about decades of inflammation," Lumeng says.