Trying to break the link between obesity and poor health


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Being obese isn’t necessarily unhealthy. But most people who are obese wind up with heart disease, Type 2 diabetes and other serious medical problems. Scientists are trying to figure out how those extra pounds cause the body’s biological systems to go haywire so that they can disrupt the process.

Researchers have been zeroing in on a protein called plasminogen activator inhibitor-1, or PAI-1, whose main function seems to be preventing the breakdown of blood clots. But it has also been linked to insulin resistance, and people who are obese make more of it than people of normal weight.


Now researchers from Albert Einstein College of Medicine and the University of Texas Southwestern Medical Center report that they have figured out where that extra PAI-1 comes from: free fatty acids that are released into the bloodstream when the body breaks down fat cells for energy.

Obese people have more fat cells, so they wind up with more free fatty acids. Those acids make it harder for the liver to deal with blood sugars, which in turn makes the body less sensitive to insulin and results in diabetes.

To test their theory, the researchers recruited 30 volunteers who were overweight but healthy. They infused free fatty acids into the volunteers’ blood until the levels were the same as in obese people with diabetes. Sure enough, the volunteers wound up with elevated levels of PAI-1 and lost their insulin sensitivity.

But how did the free fatty acids lead to higher levels of PAI-1? The researchers took biopsies of the volunteers’ abdominal fat and found that the higher concentration of free fatty acid prompted a certain kind of immune system cell to make more PAI-1. Presumably, reducing free fatty acids in the bloodstream would make obesity less hazardous to one’s health.

The study was published Wednesday in the journal Science Translational Medicine.

-- Karen Kaplan