Trehalose
Trehalose prevents fructose – thought to be a major contributor to nonalcoholic fatty liver disease – from entering the liver and triggers a cellular housekeeping process that cleans up excess fat buildup inside liver cells. Nonalcoholic fatty liver disease, a condition closely linked to obesity, affects ~25% of people in the U.S. There is no drug treatment for the disease, although weight loss can reduce the buildup of fat in the liver.
“In general, if you feed a mouse a high-sugar diet, it gets a fatty liver,” said Brian J. DeBosch, MD, PhD, a pediatric gastroenterologist. “We found that if you feed a mouse a diet high in fructose plus provide drinking water that contains 3% trehalose, you completely block the development of a fatty liver. Those mice also had lower body weights at the end of the study and lower levels of circulating cholesterol, fatty acids and triglycerides.”
NALFD develops as the liver works hard to process dietary sugar, especially fructose, found naturally in fruit but also added as high-fructose corn syrup to soft drinks and many processed foods. Ultimately, the body stores fructose in the liver as triglycerides. In severe cases fat can build up to toxic levels that may eventually require a liver transplant.
Trehalose is a natural sugar found in plants and insects and consists of 2 glucose molecules bound together. More research is required before trehalose could be tested in people with nonalcoholic fatty liver disease as part of a clinical trial. “We need more studies to make sure they were not losing bone or muscle mass.” In the meantime, DeBosch advises his patients to avoid foods with added fructose, especially sugar-sweetened beverages.
A protein on the surface of liver cells: GLUT8 is required for mice to develop fatty livers in response to a high-fructose diet.
“We knew that GLUT8 carries large amounts of fructose into liver cells,” DeBosch said. “So we looked for things that block GLUT8. We were interested in investigating trehalose because it has been studied in models of neurodegenerative disorders such as prion disease or amyotrophic lateral sclerosis… In mice, trehalose appears to cause brain cells to swallow up abnormal proteins that accumulate in these conditions. We wondered if it would do the same for fat buildup in liver cells.”
They showed trehalose blocks the transport of energy in the form of sugar into liver cells, causing the cells to behave as if they’re starving. When a cell is in a state of starvation, it can turn on a process called autophagy, and begins to consume the fat already stored in the cell. But the process is not specific to fat and can drain cells of proteins, sugars and other waste.
“We appear to be hijacking the liver’s own starvation pathway using a sugar already found in nature,” DeBosch said. “We think autophagy may be triggered when the cell is stressed with too much fat or protein buildup. The cell turns on autophagy in response to the stress or because of a lack of energy and starts gobbling stuff up. It’s a house cleaning.”
The potential for this treatment strategy goes further than neurodegenerative and metabolic diseases. “Autophagy plays numerous roles in the body, ranging from healthy development to involvement in cancer and autoimmunity,” DeBosch said. “The hope is that by studying this ‘nutraceutical’ and its actions, we can uncover and then leverage its important cellular activities to halt or reverse disease.” https://medicine.wustl.edu/?p=17676&preview=1&_ppp=7302f69dfd
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