Obesity affected more than 40% of U.S. adults between August 2021 and 2023, according to Virginia Commonwealth University (VCU), and many of today’s treatments work mainly on appetite.
Two separate research teams are now looking elsewhere, at how fat cells use energy and store it. One of them, at VCU, reports that targeting a single enzyme inside mouse fat cells led to significantly lower body weight.
The researchers also think the approach could one day affect cancer risk. First, though, the fine print: everything described below comes from lab animals or cells grown in a lab, and no person has been treated.
A second project from the Weizmann Institute of Science introduces a different protein nicknamed Mitch and a few hard-to-ignore numbers.
Both teams faced the same tricky question: how do you change what fat cells do without disturbing everything else in the body?
What the VCU Team Found in Those Mice
The target is an enzyme called SPHK2, and the team targeted it in just one cell type.
SPHK2 is short for sphingosine kinase 2. It produces a signaling molecule that carries messages inside and outside cells, and it has been tied to inflammation and several cancers, liver cancer in particular.
In a study published in Science Advances and highlighted by VCU this week, lead author Ryan D. R. Brown and colleagues targeted SPHK2 only in adipocytes, the technical word for fat cells. Beyond lower weight, the mice showed better glucose tolerance, better insulin sensitivity, and less fat building up in the liver. VCU’s announcement does not say how big those changes were, how many mice were studied, or how long the work ran.
So why look for another option? Coauthor Christopher Green, who studies cancer biology at VCU, pointed to the limits of current drugs.
“GLP-1s are well established to help reduce body weight. However, they don’t work for everyone. And once you stop taking it, the weight may come back,” he said.
Where Cancer Enters the Picture
Body fat sends out hormones and signals linked to cancer, which is the connection VCU wants to test.
VCU points to several routes. Fat tissue makes extra estrogen, which is associated with higher risks of breast, endometrial, and ovarian cancers, and people with obesity often carry higher levels of insulin and a related growth factor linked to cancers including colorectal, thyroid, and prostate. Chronic inflammation can also promote tumor growth.
SPHK2 had already shown up in earlier VCU work. When researchers deleted it across the whole body of male mice, the animals were protected from obesity brought on by a Western diet and had less liver cancer.
The new study reports metabolic gains, and no cancer results have been shared for this experiment. Green says targeting fat cells could become a strategy to treat obesity and affect cancer susceptibility, but for now that remains a hypothesis.
Related: 8 Scary Complications Doctors Link to Obesity
Then There Is Mitch
The Weizmann team came to fat cells after first studying mouse muscles.
The protein, formerly MTCH2, is linked to mitochondrial fusion and energy use. Earlier Weizmann work found that mice with less MTCH2 in their muscles burned more energy, had better endurance, and resisted diet-induced obesity.
Professor Atan Gross and doctoral student Sabita Chourasia led the fat cell study, published in The EMBO Journal in January 2025. A second paper, in Nature Communications, followed up. In human cells, the team tracked more than 100 metabolic substances every few hours after deleting Mitch, and the cells burned more fats, carbohydrates, and amino acids.
The Cells That Would Not Become Fat Cells
Most cells lacking the protein stalled, and the mouse results pointed in the same direction.
In a line of mouse precursor cells, about 80% to 90% of normal cells matured into fat cells within six days. Among cells lacking Mitch, only about 5% to 10% did. Gross said those cells run short of both energy and the building materials the process needs.
Then came whole animals. Mice missing MTCH2 only in their fat cells gained weight at a normal pace on a regular diet. On a high-fat diet, they gained less weight and had less body fat than control mice, even though they ate about the same amount and didn’t exercise more.
They also used more energy, had better glucose tolerance, and showed lower cholesterol. Their lean mass, which includes muscle and other tissues, stayed comparable.
For context, a 2026 analysis of 20 clinical trials attributed about 25% to 39% of weight lost on several widely used weight-loss medicines to lean mass, and similar proportions have been reported with lifestyle changes.
Why Nobody Is Calling This a Treatment
Image credit: tirachard/123RF
A few clear lines separate these results from anything a patient could use.
Start with the cells. The fuel burning was measured in human cells grown in a lab, while the failure to form fat cells showed up in cells from mice. That second result does not show that blocking MTCH2 would stop new fat cells from forming in people, and gaining less weight on a high-fat diet is not the same as losing weight.
Safety is the bigger question. MTCH2 also helps regulate mitochondria and cell survival pathways, so blocking it everywhere could have unwanted effects.
Healthy fat tissue stores excess energy, helps keep blood sugar steady, and produces hormones, and preventing fat cells from forming could push fat into organs where it can cause harm. No such harm was shown in these experiments.
SPHK2 has its own set of problems. Its effect on tumors varies by tissue, and the VCU team says current inhibitors cause off-target effects.
What Happens Next
Before any patient is involved, the researchers want sharper tools.
The VCU team plans to keep studying SPHK2 in obesity and cancer, with funding from the National Institutes of Health and the VCU Accelerate Fund.
It hopes to find inhibitors that hit the enzyme more specifically. Green also wants treatments that can aim at particular fat depots, which he says could reduce obesity and related conditions, cancer included, while limiting unwanted side effects.
No clinical trial date or regulatory decision has been announced for either project, and nothing in these studies would change or stop a prescribed medication.
The Weizmann work adds one more possibility: therapies that alter how cells use energy could complement treatments that mainly affect appetite. Neither project reports a direct comparison with GLP-1 drugs, so whether that pairing would ever help patients remains an open question.
For a future obesity treatment, what would matter most to you: results that last after you stop, or the fewest side effects?
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