Obesity is one of the leading causes of mortality and morbidity.
It is a global epidemic that increases the risk of many problems, including heart disease and fatty liver disease (MASLD).
The number of cases of these conditions has increased as the world adopts increasingly high-energy diets and sedentary lifestyles.
Nitric oxide is a gas molecule with pleiotropic activity in the body, meaning that it affects multiple physical properties through its binding to proteins. Too much or too little nitric oxide binding (to important 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 new enzyme (SCoR2) that removes nitric oxide from proteins that control fat accumulation. 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 and prevented weight gain and liver damage.
“We have a new class of drugs that prevents weight gain and lowers cholesterol – a potential therapy for obesity and cardiovascular disease, with additional benefits for the liver,” said the study’s lead author, Jonathan Stamler, MD, president and co-founder of Harrington Discovery Institute, Distinguished University Professor, Robert S. and Sylvia K. Reitman Family Foundation Professor of Cardiovascular Innovation, and professor of medicine and biochemistry at University Hospitals and Case Western Reserve University.
“In the liver, nitric oxide inhibits the proteins that create fat and cholesterol. In adipose tissue, nitric oxide inhibits the genetic program that produces the enzymes that create fat,” added Dr. Stamler added.
Dr. Describing the research team’s ambition, Stamler said: “Our team looks forward to further developing a first-in-class drug to block weight gain and lower cholesterol, with beneficial effects on liver health.”
The drug will be developed with the help of UH’s Harrington Discovery Institute, which has a unique mission: accelerating promising drug discoveries for unmet needs.
