Published on: Dec 23, 2025
Obesity has become a global epidemic and a leading cause of illness and death, driven by rising rates of heart disease and metabolic dysfunction–associated fatty liver disease (MASLD) as energy-dense diets and sedentary lifestyles become more common worldwide.
Nitric oxide is a signaling gas with wide-ranging effects in the body, acting through its binding to proteins. Both excessive and insufficient nitric oxide–protein interactions can disrupt normal physiology and lead to disease.
University Hospitals and Case Western Reserve University identified a previously unknown enzyme, SCoR2, that removes nitric oxide from proteins involved in fat accumulation. This removal activates fat synthesis, demonstrating that SCoR2 plays a critical role in fat production.
By genetically inhibiting SCoR2 and developing a drug to block its activity, the team showed that suppressing this enzyme prevented weight gain and liver damage in mouse models. Notably, the same drug also reduced levels of “bad” cholesterol.
“This represents a new class of therapy that both limits weight gain and lowers cholesterol, offering a promising approach for treating obesity and cardiovascular disease while also benefiting liver health,” said lead author Jonathan Stamler, MD, of University Hospitals and Case Western Reserve University.
Dr. Stamler explained that in the liver, nitric oxide suppresses proteins responsible for fat and cholesterol production, while in adipose tissue it blocks the genetic programs that drive fat-making enzymes.
The researchers plan to advance the drug into clinical trials within the next 18 months. Development will be supported by the Harrington Discovery Institute at University Hospitals, which focuses on accelerating scientific discoveries into therapies for unmet medical needs.
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