Drugs such as Ozempic, Wegovy, Mounjaro, and Zepbound have changed the way doctors treat obesity and type 2 diabetes.
These medicines can help people lose a large amount of weight by reducing appetite, slowing digestion, and helping the body control blood sugar.
These treatments belong to a group often called GLP-1 medicines. Some newer drugs, such as tirzepatide, act on more than one hormone pathway, but they are often discussed alongside GLP-1 drugs because they have similar effects on appetite and weight.
The benefits can be impressive, but the medicines are not perfect. Some people develop nausea, vomiting, constipation, or other stomach problems, and eating much less can sometimes make it harder to get enough protein, vitamins, and minerals.
Rapid weight loss can also reduce muscle as well as fat. This is important because muscle helps people stay strong, active, and independent, especially as they get older.
Researchers at the University of California, Berkeley are exploring a very different way to treat obesity and related diseases. Instead of mainly helping people eat less, they are testing a compound that appears to make the body use more energy.
The study was published on August 21 in Science Advances. The researchers examined a compound called 5-tetradecyloxy-2-furoic acid, better known as TOFA.
TOFA was first discovered decades ago and is known to interfere with the body’s production of certain fats. It belongs to a group of compounds that block an enzyme involved in making fatty acids.
Previous drugs that act on this pathway have not become standard treatments for obesity or metabolic disease. One problem is that some can unexpectedly raise triglycerides, a type of fat in the blood that is linked to heart and blood vessel risk.
The Berkeley team found that TOFA behaved differently in mice. It reduced the production of fat while also switching on genes that encourage cells to burn more fat for fuel.
This second effect appears to be especially important. The researchers found that the animals used more energy even though they did not become more active and their body temperature did not rise.
Energy use increased by as much as 18% in some experiments. In simple terms, the mice were burning more fuel without having to move more.
The treated mice also showed improvements in several signs of metabolic health. Their bodies responded better to insulin, their blood sugar control improved, and their triglyceride levels fell.
TOFA also improved signs of fatty liver disease. This condition happens when too much fat builds up in the liver and is closely linked with obesity, insulin resistance, and type 2 diabetes.
Another encouraging result involved body composition. Obese mice treated with TOFA lost body fat without showing a major loss of lean muscle.
This could be important if a similar effect were ever confirmed in people. Preserving muscle during weight loss may help reduce weakness and frailty, which are concerns for some people who lose weight quickly.
The researchers found that TOFA appears to work through more than one pathway. In addition to reducing fat production, it activates proteins called PPAR alpha and PPAR delta, which help control genes involved in burning fat and producing energy.
The team also tried to copy TOFA’s effects by giving mice two separate compounds, with one designed to reduce fat production and the other designed to increase energy use. That combination did not work as well as TOFA alone.
This suggests that TOFA may trigger a more coordinated response inside cells. Its particular mix of actions may be more important than simply combining two drugs that target the same general processes.
The researchers then tested TOFA together with existing weight-loss medicines, including semaglutide and tirzepatide. In mice, the combinations led to greater improvements in body weight, blood sugar, insulin levels, and triglycerides than either treatment used alone.
This is important because the researchers do not see TOFA as a replacement for GLP-1 medicines. Instead, they think it could eventually work alongside them by targeting the other side of the energy equation.
GLP-1 drugs mainly reduce how much energy a person takes in through food. TOFA is being studied as a way to increase how much energy the body uses.
The idea is appealing, but the research is still at a very early stage. So far, TOFA has been tested in animals, and scientists do not yet know whether it will be safe or effective in people.
Animal studies are useful for finding possible treatments, but many compounds that work well in mice do not work the same way in humans. Researchers will need to study the right dose, possible side effects, long-term safety, and whether the compound truly preserves muscle in people.
The team has created a company called ReRx Therapeutics to help move the research toward human testing. Future studies will need to show whether TOFA can provide meaningful benefits without causing new metabolic or cardiovascular problems.
Overall, the findings are interesting because they point to a different way of thinking about obesity treatment. Instead of focusing only on appetite and food intake, future therapies may also try to safely increase energy use while protecting muscle and improving blood sugar control.
The strongest part of the study is that TOFA improved several problems at the same time in mice, including obesity, insulin resistance, high triglycerides, and fatty liver. The biggest limitation is equally clear: no one yet knows whether these effects will translate to humans, so the results should be viewed as promising early research rather than evidence of a new treatment ready for patients.
Source: University of California, Berkeley.
