UC Berkeley researchers discover TOFA, a compound that boosts metabolism and burns fat. Early mouse studies show it works synergistically with Ozempic and Wegovy.
By Adam Makins · 
GLP-1 medications like Ozempic and Wegovy have revolutionized obesity and diabetes treatment, delivering impressive weight loss results for millions of patients. But they come with a catch: these drugs work by suppressing appetite, which can lead to nausea, muscle loss, and nutritional deficiencies that might increase frailty risk over time.
Now researchers at UC Berkeley have discovered something potentially game-changing. Instead of making people eat less, they’re exploring how to make bodies burn more energy. A compound called 5-tetradecyloxy-2-furoic acid (TOFA) does exactly that by ramping up metabolic activity while simultaneously reducing harmful lipids like cholesterol and triglycerides.
In mouse studies published in Science Advances, TOFA improved insulin sensitivity, glucose control, and fatty liver disease markers. Critically, obese mice lost fat without losing lean muscle mass, a significant advantage over appetite-suppressing approaches.
TOFA isn’t new. The compound was discovered back in the 1970s and belongs to a class called ACC inhibitors that block lipid production. What makes TOFA different is its dual action. Beyond suppressing lipid synthesis, it activates cellular receptors called PPARα and PPARδ that flip a metabolic switch, telling cells to burn fat for fuel and generate more energy.
The results were striking: energy expenditure increased by up to 18% without requiring mice to exercise more or raise their body temperature. This elegant simplicity has major implications. Research in diabetes has long sought interventions that increase calorie burning rather than just restrict intake, and TOFA appears to deliver that capability.
Previously, other ACC inhibitors caused unwanted triglyceride spikes that could increase cardiovascular risk. TOFA avoided this problem, likely because its combined effects on lipid production and energy metabolism work in concert rather than at cross purposes. When researchers tested whether they could replicate TOFA’s benefits using two separate compounds, the results fell short, suggesting that this particular molecular combination is genuinely important.
Here’s where things get really interesting. The Berkeley team tested whether TOFA could be combined with existing GLP-1 medications. When given together to mice, the pair produced better improvements in body weight, glucose control, insulin levels, and triglycerides than either drug alone.
“In our combination experiments, TOFA worked additively or synergistically with the GLP-1 appetite-suppressing drugs,” said Anders Näär, the study’s senior author. Rather than replacing GLP-1s, TOFA appears complementary. This matters because it suggests a potential future where patients could benefit from two distinct metabolic pathways simultaneously: reduced calorie intake plus increased energy expenditure.
The complement to appetite suppressants could also mitigate GLP-1 downsides. If TOFA preserves muscle mass while promoting fat loss, combining it with GLP-1 drugs might reduce the frailty risk associated with muscle wasting.
There’s an important caveat: all of this remains preliminary. TOFA has only been tested in animals. Human safety and effectiveness are completely unknown and will require proper clinical trials before anyone sees this drug in pharmacies.
Still, the research team is moving forward with confidence. With backing from UC Berkeley’s entrepreneurial ecosystem, including Nucleate and Berkeley SkyDeck, they’ve launched ReRx Therapeutics to shepherd TOFA toward potential patient use. Several ACC inhibitors have already reached mid-stage human trials, so the regulatory pathway exists, even if it’s lengthy and uncertain.
The obesity treatment landscape is evolving rapidly. As GLP-1 medications transform how we think about metabolic disease, compounds like TOFA could unlock entirely new therapeutic possibilities. Whether TOFA delivers on its promise in humans remains to be seen, but the concept of working with metabolism rather than against appetite represents a genuinely novel direction.
Source material provided by University of California - Berkeley
Would a dual-action drug that increases calorie burning actually succeed where appetite suppressants sometimes fail?
