Scientists found a hidden fat switch and turned it off

• Obesity and fatty liver disease are becoming more common worldwide as diets grow more calorie-dense and daily life becomes less active.
• Scientists in Cleveland have identified a previously unknown enzyme that the body needs in order to make fat.
• When researchers blocked this enzyme, it stopped weight gain and reduced unhealthy cholesterol levels.
• The discovery is now driving development of a potential three-in-one drug aimed at obesity, fatty liver disease, and heart disease.

Obesity and Fatty Liver Disease Are Rising Worldwide

Obesity has become a global health crisis and a leading contributor to illness and early death. It raises the risk of serious conditions such as heart disease and fatty liver disease (MASLD). As diets have shifted toward calorie-dense foods and daily life has become more sedentary, rates of these disorders have climbed steadily around the world.

Nitric oxide is a gas produced naturally in the body that influences many biological processes. It works by attaching to proteins and changing how they function. Maintaining the right balance is critical. When nitric oxide binds too much or too little to certain key proteins, it can contribute to disease.

Scientists Identify an Enzyme That Triggers Fat Production

In a new study published in Science Signaling, researchers from University Hospitals and Case Western Reserve University identified a previously unknown enzyme called SCoR2. This enzyme removes nitric oxide from proteins that regulate fat buildup. When nitric oxide was removed, fat production switched on, showing that SCoR2 is essential for making fat.

Blocking the Enzyme Prevented Weight Gain in Mice

The research team then tested what happens when SCoR2 is blocked. They did this both through genetic methods and by developing a drug designed to inhibit the enzyme. In mouse models, shutting down SCoR2 stopped weight gain and protected the liver from injury. The treatment also reduced levels of bad cholesterol.

"We have a new class of drug that prevents weight gain and lowers cholesterol -- a potential therapy for obesity and cardiovascular disease, with additional hepatic benefits," explained lead author of the study, Jonathan Stamler, MD, President and Co-Founder, Harrington Discovery Institute, Distinguished University Professor, Robert S. and Sylvia K. Reitman Family Foundation Professor of Cardiovascular Innovation, and Professor of Medicine and of Biochemistry at University Hospitals and Case Western Reserve University.

How Nitric Oxide Regulates Fat and Cholesterol

Dr. Stamler said nitric oxide acts as a natural brake on fat production in different tissues. "In the liver, nitric oxide inhibits the proteins that make fat and cholesterol. In fat tissue, nitric oxide inhibits the genetic program that makes the enzymes that create fat," he said.

Researchers now plan to move the drug toward clinical testing in people. That process is expected to take about 18 months.

"Our team looks forward to further developing a first-in-class drug to block weight gain and lower cholesterol, with favorable effects on liver health," Dr. Stamler said.

Drug Development Support and Broader Impact

The drug will be advanced with support from the Harrington Discovery Institute at UH, an organization focused on turning promising scientific findings into treatments for unmet medical needs. Now in its 13th year, the institute's expanding portfolio includes 227 medicines in development; 75 institutions supported; 46 companies launched; 24 medicines currently in clinical trials; and 15 licenses to pharmaceutical companies.