New Enzyme Discovery Could Lead to Combined Treatment for Obesity, Fatty Liver, and Heart Disease: Study Suggests - Video

Scientists based in Cleveland have identified a previously unknown biological mechanism that plays a key role in fat production, a discovery that could pave the way for a new drug targeting obesity, fatty liver disease, and heart disease simultaneously.

In a study published in Science Signaling, researchers from University Hospitals and Case Western Reserve University identified a new enzyme known as SCoR2. The enzyme regulates fat production by controlling how nitric oxide interacts with proteins involved in lipid metabolism. Nitric oxide is a naturally occurring molecule in the body that helps regulate many biological processes. When its balance is disrupted, it can contribute to disease.

Obesity is a growing global health challenge and a major risk factor for metabolic-associated steatotic liver disease (MASLD) and cardiovascular disease. Changes in diet, including higher calorie intake, along with increasingly sedentary lifestyles, have driven a steady rise in these conditions worldwide.

The researchers found that SCoR2 removes nitric oxide from key metabolic proteins, effectively switching on fat and cholesterol production. When this enzyme was blocked—either through genetic approaches or with an experimental drug—fat production was suppressed.

In mouse models, inhibiting SCoR2 prevented weight gain, reduced levels of low-density lipoprotein (LDL) or “bad” cholesterol, and protected the liver from damage associated with fat accumulation. These findings suggest that SCoR2 is essential for the development of obesity and related metabolic disorders.

According to senior author Dr. Jonathan Stamler, nitric oxide normally acts as a natural brake on fat production in both the liver and fat tissue. By maintaining this brake, blocking SCoR2 helps prevent excessive fat and cholesterol buildup.

The research team is now working to advance the SCoR2-inhibiting drug toward clinical trials in humans, a process expected to begin within the next 18 months.

If successful in humans, this first-in-class drug could offer a unified treatment approach for multiple interconnected metabolic diseases, addressing a major unmet need in modern medicine.

REFERENCE: Nicholas M. Venetos, Colin T. Stomberski, Hua-Lin Zhou, Zhaoxia Qian, Precious J. McLaughlin, Puneet K. Bansal, John Feczko, Ilya Bederman, Hoa Nguyen, Alfred Hausladen, Joseph C. Schindler, Zachary W. Grimmett, Henri Brunengraber, Richard T. Premont, Jonathan S. Stamler. The protein denitrosylase SCoR2 regulates lipogenesis and fat storage. Science Signaling, 2025; 18 (918) DOI: 10.1126/scisignal.adv0660