New Enzyme Block Halts Weight Gain in Mice Studies

Scientists at University Hospitals and Case Western Reserve University in Cleveland have found a new enzyme that helps the body make fat. In tests on mice, they blocked this enzyme and saw no weight gain even on high-fat diets. The mice also had less liver damage and lower levels of bad cholesterol.

Background

Fat storage has long puzzled researchers. For years, experts thought it mostly came down to eating more calories than the body burns. But recent work shows enzymes inside cells play a big part in how fat builds up.

This story starts with nitric oxide, a gas that affects many body processes. It binds to proteins and acts like a brake on fat making. Too much or too little of this binding leads to health problems.

The Cleveland team looked closely at proteins in fat tissue and the liver. They wanted to know what controls nitric oxide levels on these proteins. After months of lab work, they spotted an enzyme they named SCoR2. This enzyme pulls nitric oxide off key proteins, which then allows fat production to start.

Without SCoR2, nitric oxide stays bound to those proteins. That keeps the fat-making process shut down. The finding came from a study published late last year in Science Signaling. It changes how we see fat metabolism, which experts have studied for decades.

People with obesity often face fatty liver disease and high cholesterol. These issues raise risks for heart attacks and diabetes. Current treatments focus on diet, exercise, or drugs that curb appetite. But many patients struggle to keep weight off. This new discovery points to a different path: targeting enzymes directly.

Key Details

The researchers first tested SCoR2 in lab dishes with fat cells. They saw that removing nitric oxide from proteins turned on genes that build fat. Next, they moved to live animals.

Tests in Mice

They bred mice without the SCoR2 enzyme. These mice ate a high-fat diet for weeks. Normal mice on the same diet gained a lot of weight. The SCoR2-free mice did not. Their fat tissue stayed lean, much like mice on a regular diet.

The team also checked the liver. High-fat diets cause fat to build up there, leading to swelling and scars. In the test mice, livers looked healthy. No extra fat or damage showed up.

Cholesterol levels told a similar story. Bad cholesterol, or LDL, rose in normal mice on the rich diet. In the SCoR2-free group, it stayed low. Good cholesterol held steady too.

To make sure it was not just genes, the scientists developed a drug to block SCoR2. They gave it to regular mice on high-fat food. Results matched the gene tests: less weight gain, healthier livers, better cholesterol.

"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, the lead researcher and a professor at University Hospitals.

Stamler explained that nitric oxide stops proteins in the liver from making fat and cholesterol. In fat tissue, it blocks the genes that create fat-building enzymes. SCoR2 flips that switch by clearing the nitric oxide.

The study used standard mouse models for obesity research. Mice ate diets with 60% fat calories, mimicking human junk food habits. Weights were tracked weekly, and tissues checked at the end.

What This Means

Blocking SCoR2 could lead to pills that treat obesity, high cholesterol, and fatty liver at the same time. One drug might handle problems that now need separate medicines.

Right now, weight loss drugs like semaglutide help many people shed pounds. But they often cause side effects like nausea. Some patients regain weight after stopping. An enzyme blocker might work differently, acting at the cell level without changing hunger signals.

Liver disease from fat buildup affects millions. In the US alone, over 30% of adults have it. No approved drugs fix it yet. If SCoR2 drugs work in people, they could fill that gap.

Heart disease kills more people than any other cause. High bad cholesterol clogs arteries. Lowering it saves lives. Adding weight control and liver protection would make these drugs stand out.

The team plans human tests soon. Drug development usually takes years, but this one moves fast with help from a research institute. Early safety checks could start in 18 months.

Experts outside the study say the work looks solid. Mouse results often predict human outcomes in metabolism research. Still, people are not mice. Differences in diet, genes, and lifestyle mean more study is needed.

This finding builds on other enzyme work. For example, researchers in France found surprises in how another fat enzyme, HSL, works in cell centers. That protein helps keep fat cells healthy, not just break down fat. Together, these studies show fat control is more complex than simple calorie math.

Patients with rare fat-loss conditions, called lipodystrophy, lack certain enzymes. They have low fat but high blood sugar and cholesterol. The SCoR2 work explains some of that and suggests fixes.

Drug companies will watch closely. Success here could spark a wave of enzyme-targeted treatments. For now, the best advice stays the same: eat well, move often, see a doctor for personal risks.

Stamler and his group aim to launch trials soon. They see this as a first-of-its-kind medicine. If it pans out, everyday health could shift for millions facing weight struggles.