UC Berkeley Researchers Publish Study on TOFA for Obesity and Metabolic Disease
Researchers at UC Berkeley have published a new study exploring the molecular compound TOFA as a potential alternative or complement to GLP-1 medications. The findings, published on August 21 in Science Advances, highlight how the compound increases energy expenditure and improves metabolic health in mice.
Researchers based at UC Berkeley have published a study in the academic journal Science Advances on August 21 detailing the investigation of the molecular compound TOFA as a potential alternative or complement to GLP-1 medications. The scientific inquiry focuses on treating obesity and metabolic disease by addressing energy expenditure rather than just appetite suppression.
Anders Näär, a professor of metabolic biology and nutrition, outlined the physiological basis of the research by explaining the fundamental levers of human body weight. According to Anders Näär, body weight responds to two levers, which involve taking in fewer calories or spending more energy. Anders Näär noted that GLP-1 medications work almost entirely on the first lever, prompting the research team to go after the second lever.
Justin Y. Lee, a postdoctoral student at UCSF and former Ph.D. student at Berkeley, elaborated on the specific biological mechanisms observed during the investigation. Justin Y. Lee stated that TOFA appears to engage a coordinated metabolic response. Justin Y. Lee further explained that it is not simply blocking lipid synthesis, but is also activating energy expenditure pathways that may help the body handle excess lipid and glucose more effectively.
TOFA, which stands for 5-tetradecyloxy-2-furoic acid, was initially discovered in the 1970s and belongs to a class of compounds known as ACC inhibitors. The scientific evaluation revealed that TOFA interferes with the production of lipids while simultaneously activating genes that encourage cells to use fat for fuel. During experiments conducted on mice, energy use increased by as much as 18 percent following administration of the compound.
In addition to increased energy expenditure, the mouse experiments demonstrated multiple health improvements related to metabolic function. Specifically, TOFA improved insulin sensitivity, enhanced glucose control, reduced triglycerides, and improved signs of fatty liver disease. Crucially, these metabolic improvements occurred without causing any significant reduction in lean muscle mass.
Building upon the potential clinical applications of these findings, the researchers created a company called ReRx Therapeutics to help move the research toward potential patient use. Addressing how TOFA might fit into existing treatment landscapes, Anders Näär stated that in their combination experiments, TOFA worked additively or synergistically with the GLP-1 appetite-suppressing drugs, leading the team to view it as complementary rather than as a replacement.
The published study was supported by a wide network of institutions and contributors. The list of people involved in the research includes Justin Y. Lee, Chi Zhu, Melissa A. Boldridge, Rachelle L. Stark, Lei Xu, Federico Gonzalez, Xin Tang, Kaitlyn T. Dang, Kook Son, Gracia Bonilla, Kashish Chetal, Ruslan I. Sadreyev, Kosuke Watari, Michael Karin, Christina Papa, Bilal N. Sheikh, and Prabha Ibrahim. Associated organizations span UC Berkeley, Science Advances, UCSF, ReRx Therapeutics, Nucleate, Berkeley SkyDeck, UCSF Liver Center, University of Michigan Animal Phenotyping Core, Massachusetts General Hospital, University of California, San Diego, and the Helmholtz Center Munich.
