TOFA, a decades-old oral compound identified by UC Berkeley-led researchers, cut body weight in obese male mice by an average 18% without reducing food intake or causing statistically significant lean-mass loss.
The drug worked by boosting energy expenditure rather than suppressing appetite: treated mice burned up to 18% more energy, while researchers said TOFA blocks lipid-production enzymes and activates fat-burning cellular pathways.
Combined with semaglutide or tirzepatide, TOFA produced greater weight loss and better blood sugar, insulin and triglyceride measures than either drug alone; after treatment stopped, TOFA-treated mice stayed near control weights while semaglutide mice regained rapidly.
The compound also improved signs of MASH in mice, reducing liver fat, inflammation and fibrosis without raising blood triglycerides, a problem that has hindered some similar metabolic drugs.
Human use remains untested: the study involved only male mice, long-term safety and dosing are unknown, and outside experts cautioned that obesity is complex and promising mouse results may not translate cleanly to people.