Researchers at Massachusetts General Hospital have found an unexpected link between electron imbalances in liver cells and many metabolic problems that increase the risk of conditions such as cardiovascular disease and fatty liver disease.. Their results, published in the journal Nature, shed light on a phenomenon known as reduction stress and how genetic and environmental factors such as diet influence this risk factor for disease, according to the online publication for girls and women.. net Stress reduction occurs when cells accumulate an excess of electrons, which play an important role in energy production. " “But if there is an imbalance between supply and demand for these electrons, in particular an oversupply, you can reduce stress.”.

Eating a high-fat diet and drinking alcohol can stress your liver cells. Although reductive stress has been associated with some rare genetic disorders known as mitochondrial diseases, its role in more common conditions has not been well understood..

Moota's colleague and lead author of the study, Hepatologist General Russell Goodman, MD, led the team that administered the genetically engineered LbNOX enzyme to the livers of lab mice given alcohol.. “Alcohol generates a ton of electrons and that causes a lot of stress,” Goodman says.. And yet, LbNOX prevented the development of restorative stress in mice.. “The study showed that we can use this genetic tool to control restorative stress in the liver,” he says.. "

The team identified a blood metabolite called alpha-hydroxybutyrate that increased when electrons accumulated in liver cells.. This intrigued researchers, as alpha-hydroxybutyrate levels are associated with insulin resistance, a risk factor for type 2 diabetes, and obesity.. Previous genetic analysis has linked alpha-hydroxybutyrate levels in humans to a variant in a gene called GCKR, which occurs in about 50 percent of people and appears to affect the risk of many diseases and unhealthy traits, such as fatty liver and elevated blood fat levels.. They showed that a GCKR mutation in mouse liver cells was associated with high levels of alpha-hydroxybutyrate, linking it to restorative stress..

Importantly, this study (funded by the Marriott Foundation) found that treating restorative stress with LbNOX reduced triglycerides, which increase the risk of cardiovascular disease, and improved metabolic factors, including insulin resistance..

Mootha believes that alpha-hydroxybutyrate could be used as a biomarker to test for reduction stress, and that LbNOX could one day be a treatment for diseases caused by metabolic dysfunction.. “LbNOX empowers a new class of research we call causal metabolism,” Muta says.. “They allow us to control metabolism in living organisms for the first time and see what the consequences are.”.

medical-heal. en.