Researchers at UT Southwestern Medical Center have identified a protein that may help explain why some people are healthy despite being obese.
In the study, they found that fat but healthy mice lacked a protein called collagen VI, which normally surrounds fat cells and limits how large they can grow, like a cage around a water balloon.
They found that mice whose fat cells were allowed to grow larger than fat cells in normal mice developed ''healthy'' obesity when fed a high-fat diet.
"The mice lacking collagen VI fared much better metabolically than their counterparts that retained this particular collagen," said Dr. Philipp Scherer, director of the Touchstone Center for Diabetes Research at UT Southwestern and the study's senior author.
"The mice without collagen VI don't develop inflammation or insulin resistance. They still get obese, but it's a ''healthy'' obesity," he added.
When people take in more calories than needed, excess calories are stored in adipose or fatty tissue.
The fat cells are embedded in and secrete substances into an extracellular matrix, a type of connective tissue that provides support to fat tissue, like scaffolding.
Collagen VI is one component of the extracellular matrix. Too much of this connective tissue prevents individual cells from expanding and can lead to fibrosis and eventually inflammation.
Dr. Scherer said that inflammation is thought to be an underlying cause of metabolic disorders in humans.
He said that large fat cells are often considered a bad omen because they typically lead to increased cell death and systemic insulin resistance.
Under normal circumstances, fat cells continue to grow until they reach a point where the extracellular matrix they've built around themselves is so strong that it's no longer flexible.
"In this particular case, however, the large fat cells are not as inflamed as they would normally be. Fat cells that lack collagen VI can grow to a huge size without becoming inflamed, suggesting that collagen VI directly affects the ability of fat cells to expand," Dr. Scherer said.
According to Dr. Scherer, the current finding is clinically relevant and probably will translate well from the mice to humans.
"Our study highlights the fact that collagen VI, and possibly other extracellular matrix constituents, are extremely important in modulating fat-cell physiology," he said.
The study appears online and in a future edition of Molecular and Cellular Biology.