Obesity is one of the major causes of mortality as well as morbidity.
It’s a global epidemic that increases the risk for many problems including heart disease and fatty liver disease (MASLD).
Rates of these disorders have risen as the world increasingly adopts energy-dense diets and sedentary lifestyles.
Nitric oxide is a gas molecule with pleiotropic actions in the body, meaning that it influences multiple physical traits through its binding to proteins. Too much or too little nitric oxide binding (to key proteins) causes disease.
In a new study, published December 23 in the AAAS journal, Science Signaling, a research team from University Hospitals and Case Western Reserve University discovered a novel enzyme (SCoR2) that removes nitric oxide from proteins that control fat build up. Removal of nitric oxide turned on fat synthesis, establishing that SCoR2 is needed to make fat.
The research team then inhibited SCoR2 genetically and by developing a drug. After testing it on mouse models, they found that blocking this nitric oxide-removing enzyme lowered bad cholesterol, prevented weight gain and liver injury.
"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.
"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," Dr. Stamler added.
Describing the ambition of the research team, Dr. Stamler stated, "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.”
The drug will be developed with the help of Harrington Discovery Institute at UH, which has a singular mission: To accelerate promising discoveries into medicines for unmet needs.
