Fruit flies are good for such research insights in large part because of the insects' short life span - about 30 days - meaning their development and biological processes are more easily observed than in other, longer-lived models, such as mice. Fruit flies also are easy to manipulate genetically and are less expensive to study compared to mice or other models, according to Thummel. In addition, the mechanisms by which metabolism is controlled in fruit flies are very similar to those in mice or humans.

"We can do a lot more mechanistic studies in a fly than are possible in a mouse," he says. "We can study metabolic pathways faster and more in-depth."

Along with its important role in helping to maintain proper levels of cholesterol, DHR96 also plays an integral part in regulating dietary fat metabolism, Thummel and another U of U researcher report in a Dec. 2 study in Cell Metabolism.

In flies in which DHR96 was silenced, TAG levels were markedly reduced in the intestine, making the insects resistant to diet-induced obesity. But when DHR96 was overexpressed, meaning there were higher levels of the protein, it led to increased TAG levels and made the flies more prone to being overweight. These findings show that DHR96 is required for breaking down dietary fat in the intestine of fruit flies and provide insight into how dietary fat metabolism is regulated in Drosophila.

"This nuclear receptor plays a major role in sensing and regulating cholesterol and TAG uptake in the intestine in fruit flies," Thummel says. "It functions similarly to the way LXR functions in humans, although we have a relatively poor understanding about how LXR controls these pathways."

In his future studies, Thummel intends to learn more about how DHR96 regulates metabolism by studying the functions of the genes that it controls.

Source: University of Utah Health Sciences