Fat-Regulating Enzyme Offers New Target for Obesity

Key Highlights (Quick Summary)

• Researchers identified SCoR2, a novel Fat-Regulating Enzyme that is synthesised via nitric oxide signaling.
• Blocking SCoR2 prevented weight gain, liver injury, and high LDL cholesterol in mouse models.
• Findings suggest a first-in-class obesity and cholesterol therapy with liver-protective benefits.
• Drug candidates are expected to enter clinical trials within 18 months

Understanding the Role of a Fat-Regulating Enzyme in Obesity

Obesity remains a global public health challenge, driving increased rates of cardiovascular disease and metabolic-associated steatotic liver disease (MASLD). Despite multiple treatment options, long-term weight control and lipid regulation continue to be unmet clinical needs.

In a study published on December 23 in Science Signaling, researchers from University Hospitals and Case Western Reserve University identified a previously unknown enzyme, SCoR2 (S-nitrosylation Co-Regulator 2), that plays a central role in fat synthesis.

Nitric oxide (NO), a biologically active gas molecule, regulates metabolism by binding to proteins that control fat and cholesterol production. Balanced nitric oxide signaling is essential, as both excess and deficiency are associated with disease states. The newly identified enzyme SCoR2 removes nitric oxide from metabolic proteins, thereby activating fat synthesis pathways.

This discovery positions SCoR2 as a critical molecular switch in metabolic regulation.

Blocking the Fat-Regulating Enzyme Prevents Weight Gain and Liver Injury

To explore therapeutic potential, researchers inhibited the fat-regulating enzyme using both genetic approaches and a newly developed drug compound. In mouse models, blocking SCoR2 prevented weight gain, even under conditions that typically promote obesity.

Beyond weight control, inhibition of the fat-regulating enzyme also demonstrated significant liver protection, reducing injury linked to fatty liver disease. These findings are particularly relevant for clinicians managing patients with overlapping obesity, dyslipidemia, and hepatic disease.

The study further showed that pharmacologic inhibition of SCoR2 lowered LDL cholesterol levels, suggesting cardiovascular benefits in addition to metabolic effects. According to lead author Jonathan Stamler, MD, nitric oxide normally suppresses fat- and cholesterol-producing proteins in the liver and inhibits fat-producing gene programs in adipose tissue. By removing nitric oxide, SCoR2 enables both fat and cholesterol synthesis, making it a high-value therapeutic target.

Clinical Implications and Drug Development Outlook

This discovery introduces a first-in-class therapeutic strategy that differs from appetite suppressants or nutrient absorption blockers. Instead, targeting a fat-regulating enzyme directly addresses intracellular metabolic signaling, which may offer more durable and physiologically aligned outcomes.

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With support from the Harrington Discovery Institute, the research team plans to advance the SCoR2 inhibitor into clinical trials within approximately 18 months. If successful, this approach could represent a meaningful shift in obesity and lipid disorder management.

For healthcare professionals and nurses, these findings reinforce the growing importance of nitric oxide biology and enzyme regulation in metabolic disease and point toward new clinical tools for managing obesity-related complications.

Source:

University Hospitals Cleveland Medical Center