Medicines such as Ozempic, Wegovy, Mounjaro and Zepbound have changed how obesity and diabetes are treated by helping people control appetite, blood sugar and body weight. Now, researchers at UC Berkeley are exploring a different approach — helping the body burn more energy rather than simply reducing how much a person eats.
The study, published in Science Advances, examined a compound called 5-tetradecyloxy-2-furoic acid (TOFA).
A different way to tackle obesity
Researchers found that TOFA can block the production of certain lipids, including cholesterol and triglycerides, while also activating genes involved in burning fat and producing energy.
In experiments involving mice, the compound improved insulin sensitivity and glucose control, lowered triglycerides and improved features associated with fatty liver disease.
Obese mice given TOFA also lost fat without experiencing significant loss of lean muscle mass.
The body started burning more energy
The researchers found that TOFA activated cellular receptors called PPARα and PPARδ, which help cells take up and use fat for energy.
In the mice, this increased energy expenditure by up to 18% without increasing physical activity or body temperature.
Researchers said this dual action could explain why TOFA avoided the rise in triglycerides associated with some earlier compounds designed to block lipid production.
Could it work alongside GLP-1 medicines?
The researchers also tested TOFA alongside medicines such as semaglutide and tirzepatide, the active drugs marketed as Ozempic and Wegovy, and Mounjaro and Zepbound respectively.
In mice, combining TOFA with these GLP-1 medicines produced greater improvements in body weight, glucose control, insulin levels and triglycerides than either treatment alone.
Researchers therefore see TOFA as a possible complementary approach rather than a replacement for GLP-1 medicines.
Human trials are still needed
There is an important limitation: TOFA has so far been studied only in animals.
Its safety and effectiveness in humans have not yet been established, meaning the findings cannot currently be considered evidence that the compound will treat obesity or diabetes in people.
Researchers have founded ReRx Therapeutics to help advance the work towards potential human applications.
The study nevertheless offers a different direction in metabolic research — one that focuses on increasing the body’s energy expenditure while potentially preserving muscle, rather than relying primarily on appetite suppression.