Sugar may be the villain of our time, with too much of the sweet stuff known to be a leading cause of developing diabetes. But now researchers at Washington University School of Medicine in St. Louis have discovered a new way to reduce the risk of this condition – sugar. Trehalose is a natural sugar that has now been found to deprive the liver of glucose and activate a gene that improves insulin sensitivity and triggers the burning of more fat.
A comparison of the livers of different groups of mice – left is a healthy mouse liver, middle shows the fatty deposits (red) left by a high-fat/cholesterol diet over 12 weeks, and the right image shows that same high-fat diet in mice with high levels of Aloxe3 expression(Credit: Brian Debosch)
Metabolic syndrome, a group of related conditions including obesity, diabetes and fatty liver disease, is one of the main health concerns of our time. Diets high in sugars and fats are the main culprits, as the body struggles to keep up with increased levels of glucose in the bloodstream. Eventually, the body stops responding to insulin – the hormone that processes glucose into energy – and in turn that insulin resistance can lead to type 2 diabetes.
Although more sugar might seem counterintuitive, trehalose could hold the key. This natural sugar is made up of two glucose molecules, and in the past it’s been found to help clear up atherosclerosis. In the new study, the WUSTL team investigated trehalose as a possible treatment for metabolic disease, by dosing the drinking water of test mice and seeing which genes were activated in their livers.
Mice that received trehalose were found to have a whole range of positive effects. They made better use of their natural insulin, burned more calories, had a higher body temperature, gained less weight, accumulated less fat (particularly in the liver) and had fewer fats and cholesterol biomarkers in their blood. Interestingly, trehalose-laced drinking water even protected mice that were fed a diet that would induce obesity, and those that were genetically prone to obesity.
The key, the researchers discovered, was a gene called Aloxe3, which trehalose activates by reducing the amount of glucose that reaches the liver. That leads to the health benefits seen in the test mice, but the sugar isn’t the only way to do it – by giving another group of mice nothing but water for a two day period, the team found that fasting seems to use the same means for the same effect.
“We learned that this gene, Aloxe3, improves insulin sensitivity in the same way that common diabetes drugs – called thiazolidinediones – improve insulin sensitivity,” says Brian DeBosch, an author of the study. “And we showed that Aloxe3 activation in the liver is triggered by both trehalose and by fasting, possibly for the same reason: depriving the liver of glucose. In mice, this gene is turned on as part of what seems to be the normal fasting response. Our data suggest that fasting – or giving trehalose with a normal diet – triggers the liver to change the way it processes nutrients, in a beneficial way. And if glucose can be blocked from the liver with a drug, it may be possible to reap the benefits of fasting without strictly limiting food.”
As with any advance of this kind, the researchers point out that there’s still plenty of work to do before we’re treating diabetes with spiked water. The team says that enzymes in the digestive tract may break down the trehalose molecules before they can help, although a similar sugar called lactotrehalose was tested and found to be hardier, while still delivering the same benefits.
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