New Enzyme Block Stops Weight Gain in Mice Studies

Researchers in Cleveland have identified an enzyme called SCoR2 that the body needs to produce fat. In tests with mice, blocking this enzyme stopped weight gain even on high-fat diets, reduced damage to the liver, and lowered levels of harmful cholesterol. The work points to a possible new path for treating obesity, fatty liver problems, and heart disease.

Background

Fat builds up in the body through a process where cells turn sugars and other nutrients into stored energy. For years, scientists have studied how the body handles this fat, looking at hormones, genes, and proteins that control it. Obesity affects millions worldwide, leading to extra weight, high cholesterol, and liver issues where fat clogs the organ.

This new finding centers on nitric oxide, a gas molecule that affects many body functions. It binds to proteins and changes how they work. Too much or too little of this binding can cause health problems. The Cleveland team looked at how nitric oxide ties to fat-making proteins. They found SCoR2 removes nitric oxide from those proteins, which then allows fat production to start.

Without SCoR2, nitric oxide stays on the proteins. This keeps fat-making in check. In the liver, nitric oxide stops proteins that build fat and cholesterol. In fat tissue, it blocks the genes that make enzymes for fat creation. The discovery came from lab work at University Hospitals and Case Western Reserve University. It appeared in the journal Science Signaling on December 23, 2025.

Past studies showed links between nitric oxide and metabolism, but this team pinpointed SCoR2 as a key player. They used mouse models fed high-fat food to mimic human diets that lead to weight gain. These mice normally get heavier, develop fatty livers, and see cholesterol rise. The researchers tested ways to block SCoR2 both with genes and a new drug.

Key Details

The team first turned off the SCoR2 gene in mice. These mice ate a high-fat diet but did not gain weight like normal mice. Their fat tissue stayed lean, and livers showed less fat buildup. Blood tests revealed lower levels of LDL cholesterol, the type that clogs arteries.

How They Blocked the Enzyme

Researchers developed a drug that stops SCoR2 from working. They gave it to mice on rich diets. Results matched the gene tests: no weight gain, healthier livers, and better cholesterol numbers. The drug targets the enzyme's action on nitric oxide removal precisely.

“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,” said Jonathan Stamler, lead author of the study and a professor at University Hospitals and Case Western Reserve University.

Stamler explained that in fat tissue, nitric oxide blocks the genetic setup for fat enzymes. In the liver, it curbs fat and cholesterol makers. Blocking SCoR2 lets nitric oxide do its job, keeping fat production low.

The study used standard mouse models for obesity research. Mice were fed diets with 60% fat calories for weeks. Control groups gained 20-30% body weight. SCoR2-blocked groups stayed stable. Liver scans showed 50% less fat in treated mice. Cholesterol dropped by 30-40% in blood samples.

Safety checks found no major side effects. Mice moved normally, ate as much, and had steady energy levels. This suggests the block targets fat pathways without broad harm.

What This Means

This enzyme discovery changes how we view fat storage. It shows fat making depends on specific switches like SCoR2, not just food intake. Drugs targeting it could help people who struggle with weight despite diet and exercise.

Obesity links to type 2 diabetes, heart attacks, and strokes. Fatty liver disease affects one in three adults in some places. A single drug hitting weight, cholesterol, and liver health would fill a big gap. Current drugs like statins lower cholesterol but do little for weight. Weight-loss shots help shed pounds but often raise other risks.

The team plans human trials in about 18 months. They work with Harrington Discovery Institute to speed drug development. This group has pushed over 20 medicines to clinics. Early tests will check safety in people, then effects on weight and blood markers.

Experts outside the study call it promising. One metabolic researcher noted similar enzyme paths in human cells. But mice differ from people, so results need confirmation. Long-term effects, like on muscle or bones, require more study.

For patients, this means hope for easier treatments. Imagine a pill that keeps fat in check at the cell level. It would not replace healthy habits but could make them work better. The work also sheds light on why some people store fat differently.

Broader impacts touch food industries and public health. If successful, it could cut costs for treating obesity-related ills, now over $200 billion yearly in some countries. Researchers stress steady progress: from lab to shelf takes years, but this step feels solid.

Stamler added in follow-up notes:

“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 path ahead involves dose tests, combo therapies, and diverse patient groups. Success here could reshape metabolic care.