How Obesity Abets Type 2 Diabetes

Human fat can be healthy or sick - healthy in lean people and sick in obese. And a new research effort shows sick fat cells can produce proteins that contribute to type 2 diabetes. The study, performed by researchers at Temple University, discovered that fat cells in obese people bear a great deal of stress in a cellular component called the endoplasmic reticulum, which is the cells' protein factory. The stress, says lead researcher Dr. Guenther Boden, apparently produces proteins connected with insulin resistance, a major contributor to obesity-related diabetes. In particular, 19 proteins were more abundant in obese people's fat cells than lean people's, including three that were related to a specific endoplasmic reticulum stress-related response.

In addition, the obese people's fat tissue displayed much more inflammation than normal. "This is the first human study to show that the fat in obese people is 'sick,' meaning that it does not function as it should," Boden says. He speculates that when the body continually ingests far more calories than it can use, it stresses the normal fat-production system, creating fat that is both excessive and "sick."

 "The bad health effects associated with obesity are probably not caused by the extra fat itself," he says. "They probably result from the constant overloading of the system with excess calories" - which may explain the dramatic improvement in insulin resistance in obese people immediately following gastric-bypass surgery, even before they lose any weight. The surgery may relieve the constant caloric stress on the body.

Endocrinologist and diabetes researcher R. Paul Robertson, a professor of medicine and pharmacology at the University of Washington and president-elect of medicine and science for the American Diabetes Association, says, "We really don't understand what insulin resistance is. We know it exists, but we don't have a good molecular explanation for it. Studies like this one provide important clues."


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