Berkeley researchers unveil TOFA, a compound that burns fat without muscle loss

A team led by Anders Näär at the University of California-Berkeley identified 5-tetradecyloxy-2-furoic acid (TOFA) as a multi-functional oral molecule that raises metabolic rate by as much as 18% in mice, leading to fat loss without appreciable muscle reduction. The compound simultaneously blocks lipid synthesis as an ACC inhibitor and activates PPARα and PPARδ, prompting cells to burn fat for energy, which also improves glucose control, insulin sensitivity, triglyceride levels and fatty-liver markers.

In obese mice, TOFA’s effects outperformed a two-drug regimen that separately targeted lipid production and energy expenditure, and when combined with GLP-1 drugs such as semaglutide (Ozempic/Wegovy) or tirzepatide (Mounjaro/Zepbound), it produced additive improvements in weight and metabolic health. Unlike earlier ACC inhibitors, TOFA did not raise triglycerides, likely due to its combined mechanisms. The findings, reported in Science Advances, are limited to animal models; human safety and efficacy remain to be tested. To translate the discovery, the researchers have formed ReRx Therapeutics with support from Berkeley’s Nucleate and SkyDeck programs.