Scientists at the University of California, Berkeley have identified an existing oral compound, TOFA, that produced significant weight loss in obese mice while preserving lean muscle mass. Unlike popular injectable treatments such as semaglutide, which rely heavily on appetite suppression, TOFA appears to increase the body’s energy expenditure.
How TOFA works
TOFA blocks enzymes that create lipids, including triglycerides, and activates cellular receptors that turn on genes responsible for fat burning and energy production. In laboratory tests, treated mice burned up to 18% more energy under normal and mildly warm conditions without becoming less active or developing dangerous temperature spikes.
Results in mice
The study, published in Science Advances, showed an average 18% reduction in body weight for the mice receiving TOFA, with no statistically significant loss of lean mass. When combined with existing obesity drugs such as semaglutide or tirzepatide, the compound produced even greater reductions in body weight and improvements in blood sugar, insulin, and triglyceride levels.
Importantly, mice that stopped receiving semaglutide quickly regained weight, whereas those treated with TOFA maintained weights close to control levels after the treatment ended.
Expert commentary
Dr. Leslie Pristas, a bariatric surgeon and owner of Best Life Bariatrics and Medical Weight Loss in Northeast Ohio, emphasized the importance of preserving muscle during weight loss. “Muscle mass is really important for our function during the day. It helps fight the effects of aging,” she said. “If we can avoid muscle loss while losing weight, that’s so much better.” She also warned that no single medication can permanently prevent post‑treatment weight regain, noting the complexity of obesity and the body’s weight‑set point.
Potential broader benefits
Beyond weight loss, TOFA showed promise in mouse models of metabolic dysfunction‑associated steatohepatitis (MASH), a form of fatty liver disease. Treated mice exhibited reduced liver fat, inflammation, and fibrosis without raising blood triglyceride levels—a common safety concern for similar metabolic drugs.
Next steps and cautions
The researchers acknowledge that all animal experiments involved male mice, and future studies must determine whether the results translate to female animals. Human trials have not yet begun, so the appropriate dosage, long‑term safety, and possible subtle toxicities remain unknown. As Dr. Pristas cautioned, “If it sounds too good to be true, it’s probably too good to be true.”
The study authors disclosed that several researchers hold equity in ReRx Therapeutics, a company with an option to develop the UC Berkeley TOFA discovery.
Original reporting: Fox News (HLL/CB) — read the source article.
