UC Berkeley researchers identify compound that burns fat while preserving muscle in mice

Researchers at UC Berkeley have identified a molecular compound that helps mice lose fat while preserving lean muscle mass, offering a potential new approach to treating obesity and diabetes. The compound, 5-tetradecyloxy-2-furoic acid (TOFA), was shown to improve insulin sensitivity, glucose control, and fatty liver disease markers in obese mice.

Unlike GLP-1 medications such as semaglutide and tirzepatide, which work primarily by suppressing appetite and reducing food intake, TOFA increases the body's energy expenditure. In experiments, mice treated with TOFA burned up to 18% more energy without changes in physical activity or body temperature, and they lost weight from fat tissue alone.

TOFA was first discovered in the 1970s and belongs to a class of compounds known as ACC inhibitors, which block lipid production. However, previous ACC inhibitors often raised triglyceride levels, posing cardiovascular risks. The new study found that TOFA also activates PPARα and PPARδ receptors, which turn on genes that help cells take up and burn fat for energy.

This dual mechanism appears to prevent the triglyceride increase seen with other ACC inhibitors. When researchers tested separate compounds for blocking lipid production and boosting energy expenditure, the combination was less effective than TOFA alone, suggesting its coordinated action is key.

The team also tested TOFA in combination with GLP-1 drugs and found additive or synergistic improvements in body weight, glucose control, insulin levels, and triglycerides compared to either treatment alone. Senior author Anders Näär, a professor of metabolic biology and nutrition at UC Berkeley, described TOFA as complementary to existing appetite-suppressing therapies.

The research, published in Science Advances, was conducted in mouse models only. The safety and efficacy of TOFA in humans have not yet been established. The researchers have founded a company, ReRx Therapeutics, with support from UC Berkeley's entrepreneurship programs, to advance the compound toward clinical testing.

Funding for the work came from discretionary funds at UC Berkeley, with assistance from the UCSF Liver Center and the University of Michigan Animal Phenotyping Core. Several authors, including Näär and first author Justin Y. Lee, are co-founders or equity holders in ReRx Therapeutics, which has optioned the related intellectual property.