New Experimental Treatment Burns Fat While Preserving Muscle in Obesity and Diabetes Study

Scientists at the University of California, Berkeley have identified a potential new approach to treating obesity and diabetes that could help the body burn more energy without causing the muscle loss sometimes associated with weight-loss medications.

The experimental compound, known as 5-tetradecyloxy-2-furoic acid (TOFA), works differently from widely used GLP-1 medications. Rather than primarily reducing appetite and food intake, it appears to increase the amount of energy the body uses by stimulating metabolic activity.

In a study published in Science Advances, researchers found that TOFA can suppress the production of lipids such as cholesterol and triglycerides while simultaneously activating genes involved in fat burning and energy production.

In experiments involving mice, treatment with TOFA improved insulin sensitivity and blood glucose control, reduced triglyceride levels and alleviated several features associated with fatty liver disease. Obese mice treated with the compound lost primarily fat, while their lean muscle mass remained largely unchanged.

“Body weight responds to two levers: taking in fewer calories, or spending more energy,” said senior study author Anders Näär, a professor of metabolic biology and nutrition at UC Berkeley. While GLP-1 drugs mainly affect the first mechanism, the researchers sought to target the second.

TOFA belongs to a group of compounds known as ACC inhibitors, which interfere with lipid production. Earlier drugs in this class reached clinical trials, but none has been approved for treating metabolic diseases, partly because some of them can increase triglyceride levels and potentially raise cardiovascular risks.

The Berkeley team found that TOFA appears to have an additional mechanism of action. Along with inhibiting lipid synthesis, it activates PPARα and PPARδ, receptors that regulate genes involved in the uptake and burning of fat for energy.

In mice, this dual effect increased energy expenditure by as much as 18%, without making the animals more physically active or raising their body temperature. Unlike some other ACC inhibitors, TOFA also did not cause triglyceride levels to rise.

The researchers described the compound as producing a coordinated metabolic response that both limits lipid production and activates pathways involved in energy expenditure.

The team also tested TOFA in combination with GLP-1 drugs, including semaglutide, marketed as Ozempic and Wegovy, and tirzepatide, sold as Mounjaro and Zepbound. In mice, the combination produced greater improvements in body weight, blood glucose, insulin levels and triglycerides than either treatment alone.

The researchers believe TOFA could potentially complement existing GLP-1 therapies rather than replace them.

However, the compound has so far been tested only in animals. Its safety and effectiveness in humans remain unknown, and clinical trials will be necessary before it can be considered as a treatment for patients.

To advance development of the approach, the researchers have established a company called ReRx Therapeutics.

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