Plumping Your Way to Disease

As if fat didn't give us enough trouble, a new study provides further evidence that cellulite can release disease-causing compounds. Overweight individuals generate increased amounts of a protein called monocyte chemoattractant protein-1 (MCP-1) from their fat tissue, and mice producing high levels of this protein develop insulin resistance, a precursor to diabetes.

Over the past few years, researchers have realized that fat tissue is more than just extra baggage. It excretes dozens of substances called adipokines that act as hormones and inflammatory agents (ScienceNOW, 2 April 2004). MCP-1 is one of these substances, and it tends to be elevated in the blood of people who are overweight. Numerous studies have shown that excess fat leads to insulin resistance. But evidence directly linking MCP-1 to diabetes was lacking.

So researchers from Kobe University in Japan genetically engineered mice that produce very high levels of MCP-1. They found that these mice rapidly develop insulin resistance and accumulate fat in the liver, which may lead to high cholesterol levels. The team also engineered mice that do not make the MCP-1 protein at all; these mice experience less insulin resistance and liver fat than normal mice. Finally, blocking MCP-1 activity in both normal mice and overweight mice seems to slow the development of insulin resistance, lowering the risk for diabetes, the team reports online today in the Journal of Clinical Investigation.

Experts believe that MCP-1 isn’t the only signaling molecule responsible for insulin resistance. Researchers are trying to identify these other factors and how they interrelate, says Anthony Ferrante, a diabetes specialist at the Columbia University Medical Center in New York City. Still, many are hoping that the new findings will lead to better medications to treat diabetes. "It certainly is an interesting possibility," says Philip Kern from the University of Arkansas for Medical Sciences in Little Rock. But, he says, drug development may be tricky: MCP-1 plays an important role in fighting injuries, infections, and cancer, so a drug that blocks MCP-1's actions might lead to unwanted side-effects.

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