When Temple University researchers studied fat taken from obese and lean people, they found major differences in the way fat cells from the two groups behaved.
The fat cells from the obese people showed significant stress at a part of the cell responsible for the synthesis of proteins, known as the endoplasmic reticulum (ER).
This stress appears to lead to the production of specific proteins associated with insulin resistance, which plays a major role in obesity-related diabetes, says lead researcher Guenther Boden, MD.
There was also much more inflammation in the fat tissue from the obese study participants.
"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 tells WebMD.
The job of body fat is to store excess energy, or calories.
Boden says routinely taking in more calories than the body can use not only leads to weight gain, but it also appears to stress the fat tissue to the point where it becomes fatigued and dysfunctional.
"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."
In the Temple study, Boden and colleagues performed cellular analysis on fat cells taken from the upper thighs of six normal-weight and six obese people. None of the obese study participants had diabetes.
The analysis revealed over-expression of several proteins related to energy and fat metabolism in the fat cells from obese people.
Specifically, levels of 19 proteins were higher in the fat cells from the obese people than the non-obese people, including three that were related to a specific ER stress-related response.
The researchers conclude that the endoplasmic reticulum might sense nutritional excess and translate that excess into metabolic and inflammatory responses.
Understanding Sick Cells
Boden says the findings could explain why diabetic people who have weight loss surgery often show dramatic improvements in insulin resistance within days of surgery, long before significant weight loss occurs.
"People have all kinds of theories about why bariatric surgery works the way it does, but the most simple and straightforward explanation is that the dramatic and immediate reduction in caloric intake is responsible for this improvement," he says.
Endocrinologist and diabetes researcher R. Paul Robertson, MD, tells WebMD that the findings are important because researchers have been trying to link ER stress to insulin resistance for some time.
Robertson is a professor of medicine and pharmacology at the University of Washington and the president-elect of medicine and science for the American Diabetes Association.
"We really don't understand what insulin resistance is," he says. "We know it exists, but we don't have a good molecular explanation for it. Studies like this one provide important clues."