Oral compound TOFA cuts mouse body weight about 18% without cutting appetite or lean mass

BERKELEY, Calif. - An oral compound studied at the University of California, Berkeley, cut body weight in obese mice by about 18% without reducing how much the animals ate, according to research published in Science Advances and reported by Fox News.

The molecule, known as TOFA, raised whole-body energy expenditure by as much as 18% under room-temperature and mildly warm conditions. Fox News said food intake, activity and body temperature did not show dangerous changes in the treated mice. Lean mass was largely preserved, a point researchers and clinicians flagged as important because popular GLP-1 drugs such as semaglutide often cut appetite and can cost some muscle along with fat.

TOFA works inside cells. It blocks enzymes used to make lipids such as triglycerides and turns on genes tied to fat burning and energy production. When researchers combined TOFA with semaglutide or tirzepatide, the combinations produced larger drops in body weight and better blood sugar, insulin and triglyceride readings than either approach alone. Mice that had received TOFA also held more of their weight loss after treatment stopped, while mice previously given semaglutide regained weight faster.

Dr. Leslie Pristas, a bariatric surgeon in Northeast Ohio who spoke with Fox News Digital, said muscle protects daily function and helps fight aging. She also warned against reading early animal results as a finished human drug. Obesity has many overlapping drivers, she said, and stopping a medicine abruptly can push the body back toward its prior weight set point.

The authors said all animal work used male mice, so female results are unknown. TOFA has not been tested in people. Dose, long-term safety and subtle toxicities remain open questions. Several study authors hold equity or roles in ReRx Therapeutics, which has an option on the Berkeley discovery, the paper disclosures said.