Sugars are generally not thought of as health boosters. But a new mouse study out of the Washington University School of Medicine (WUSM) shows that a natural sugar called trehalose can actually arm the immune system with more of the machinery it needs to combat atherosclerosis, a dangerous condition in which plaque build up hardens and narrows the arteries.
The researchers focussed on the ability of trehalose, a sugar consisting of two linked glucose molecules, to increase the amount of organelles inside specialized "housekeeping" cells known as macrophages. These white blood cells digest unwanted cellular material in the body and the organelles they contain help them achieve that goal. But in the case of atherosclerosis, they can get overwhelmed and actually become part of the problem.
"In atherosclerosis, macrophages try to fix damage to the artery by cleaning up the area, but they get overwhelmed by the inflammatory nature of the plaques," said senior author Babak Razani, an assistant professor of medicine at WUSM. "Their housekeeping process gets gummed up. So their friends rush in to try to clean up the bigger mess and also become part of the problem. A soup starts building up — dying cells, more lipids. The plaque grows and grows."
In their study, when the researchers injected mice predisposed to atherosclerosis with trehalose, they saw an approximate 30 percent reduction in the size of plaques in the rodents' arteries. They figured out that this was due to the fact that the natural sugar, which is found in plants, insects and some drugs, works by activating a molecule called TFEB. This molecule enters into the nucleus of macrophages, binds to their DNA and activates genes that lead to the creation of the additional organelles, turning them into "super-macrophages," according to Razani.
"Trehalose is not just enhancing the housekeeping machinery that's already there," Razani said. "It's triggering the cell to make new machinery. This results in more autophagy — the cell starts a degradation fest. Is this the only way that trehalose works to enhance autophagy by macrophages? We can't say that for sure — we're still testing that. But is it a predominant process? Yes."
With its increased ability to consume unwanted material in the arteries, the super-macrophages, might stand a chance at prevailing against plaque. Unfortunately, the study showed that trehalose only worked when it was given as an injection. The thinking is that when it is taken orally, digestive enzymes break it apart and shut down its FFEB-activating property. The researchers are currently looking for ways to overcome the enzyme and are also hopeful that trehalose could help fight other conditions including type 2 diabetes and fatty liver disease.
Their work has been published in the journal Nature Communications.
