If you fight fire with fire, you will surely get burned. But if you fight sugar with sugar, who knows what could happen?

A research team from Washington University School of Medicine has figured out the answer. In a new mice study, scientists found that a natural sugar called trehalose can be used as a weapon against fructose – a major contributor to nonalcoholic fatty liver disease.

Apparently, trehalose blocks fructose from entering the liver. The natural sugar also triggers a housekeeping process at the cellular level that cleans up excess fat that builds up inside liver cells.

Feeding a mouse a high-sugar diet will typically cause it to develop a fatty liver. However, researchers found that if the mouse is fed with high-fructose diet plus drinking water with 3 percent trehalose, the development of a fatty liver is completely prevented.

Pediatric gastroenterologist Brian J. DeBosch, one of the authors of the study, said the mice that took the 3 percent trehalose solution obtained lower body weights and lower levels of fatty acids, circulating cholesterol and triglycerides at the end of their research.

Previous studies suggest that nonalcoholic fatty liver disease builds up as the liver tries to process dietary sugar such as fructose. These sugars are naturally found in fruit, but they are also injected into soft drinks and processed food in the form of high-fructose corn syrup.

The body ultimately stores fructose in the liver as triglycerides. In severe cases of fatty liver disease, triglycerides can grow to toxic levels. The patient may eventually need a liver transplant.

Starving Liver Cells

Dietary sugar in fatty liver disease has been implicated in conditions such as obesity, high blood pressure and high insulin resistance. Researchers said it may appear counterintuitive to treat a condition that seems to be caused in part by sugar consumption with more sugar.

But in a previous study, DeBosch and his colleagues found that a protein called GLUT8, which is on the surface of liver cells, is needed by mice to develop fatty livers in response to a high-fructose diet.

GLUT8 brings high amounts of fructose into liver cells, so researchers wanted to find something that could block it. Trehalose is an interesting choice, because it had been studied in neurodegenerative disorders such as prion disease. In mice, trehalose seems to cause brain cells to swallow up abnormal proteins that accumulate in these conditions.

When the researchers tested trehalose on mice to find out its link to fatty liver disease, they found that the it blocks sugar that transports energy into liver cells. With that, the liver cells are left in a state of starvation.

Meanwhile, DeBosch hopes that other researchers turn their attention to trehalose as this treatment strategy could potentially go beyond metabolic and neurodegenerative diseases.

Trehalose

Trehalose is found in insects and plants. It is a natural sugar that consists of two glucose molecules bound together. The Food and Drug Administration has approved it for human consumption, but DeBosch said further research should be done before the natural sugar could be tested in patients with nonalcoholic fatty liver disease in clinical trials.

"I can't recommend it to my patients yet," said DeBosch. The team suspects that the weight loss in mice was the result of fat loss, but they cannot be sure that this is the only effect.

"We need more studies to make sure they were not losing bone or muscle mass," he said.

The team's findings are featured in the journal Science Signaling.

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