SALT LAKE CITYHow do fruit flies get high cholesterol and become obese? The same way as people do by eating a diet that's too rich in fats.

More importantly, according to two new studies led by a University of Utah human geneticist, fruit flies use the same molecular mechanisms as humans to help maintain proper balances of cholesterol and a key form of stored fat that contributes to obesity. The findings mean that as researchers try to learn more about the genetic and biological processes through which people regulate cholesterol and fat metabolism, the humble fruit fly, also called Drosophila, can teach humans much about themselves.

"Not a lot is known about these regulatory mechanisms in people," says Carl S. Thummel, Ph.D., professor of human genetics at the U of U School of Medicine and senior author on the two studies. "But we can learn a lot by studying metabolic control in fruit flies and apply what we learn to humans."

High cholesterol and obesity, which affects an estimated 25 percent to 30 percent of the U.S. population, are linked to heart disease, diabetes, and other diseases that take huge tolls on health and add billions of dollars to the nation's medical bills. Understanding the processes that regulate cholesterol and fat in humans could be critical for addressing those health risks in people, Thummel believes.

The two studies identify a nuclear receptor, DHR96, which plays a critical role in regulating the balance or homeostasis of cholesterol and another fat molecule called triacylglycerol (TAG). Nuclear receptors are proteins that sense the presence of chemical compounds within cells. DHR96 corresponds closely to a nuclear receptor in humans, called LXR, that is known to regulate cholesterol levels.

In a study published Dec. 2 in Genes & Development, Thummel and colleagues at the U of U and two Canadian universities show that DHR96 helps regulate cholesterol in fruit flies by binding with t
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