A promising new weight loss and diabetes treatment helps burn fat while keeping muscle
UC Berkeley researchers identified a compound, TOFA, that helps burn fat without reducing food intake or muscle mass, unlike GLP-1 drugs. The discovery, published in *Science Advances*, shows promise in mouse models for treating obesity and diabetes.
Researchers at UC Berkeley have developed a molecular compound called TOFA that increases energy expenditure in cells, helping burn fat without altering food intake or exercise levels. Unlike GLP-1 medications such as Ozempic or Wegovy, which suppress appetite, TOFA works by boosting the body’s metabolic rate. In mouse studies, the compound improved insulin sensitivity, glucose control, and fatty liver disease markers while preserving lean muscle mass. The findings suggest a potential alternative or complementary treatment for metabolic disorders. The study was published in *Science Advances* on the same day as the announcement.
The compound TOFA, first discovered in the 1970s, belongs to a class called ACC inhibitors, which block lipid production. However, unlike other inhibitors, TOFA also activates cellular receptors PPARα and PPARδ, enhancing fat burning. In mice, TOFA increased energy expenditure by up to 18% without raising triglycerides, a risk associated with other ACC inhibitors. Researchers found that TOFA’s dual mechanism—blocking lipid synthesis and activating energy-burning pathways—was more effective than using separate compounds for each function.
When combined with GLP-1 drugs like semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound), TOFA showed additive or synergistic effects in mice, improving body weight, glucose control, insulin levels, and triglycerides beyond either treatment alone. The researchers emphasize that TOFA is not intended as a replacement for GLP-1 drugs but as a complementary therapy. The study’s senior author, Anders Näär, noted that TOFA works on the second lever of body weight management—energy expenditure—while GLP-1s focus on the first—caloric intake.
The compound has only been tested in animals, and its safety and efficacy in humans remain unproven. UC Berkeley researchers, with support from local entrepreneurship programs, have founded ReRx Therapeutics to advance TOFA toward clinical trials. The work was funded by UC Berkeley, the UCSF Liver Center, and the University of Michigan Animal Phenotyping Core. Several study authors are co-founders or officers of ReRx Therapeutics, which holds rights to the UC Berkeley intellectual property related to TOFA.