Researchers at the University of California, Berkeley, have identified an old oral compound, TOFA, that produced significant weight loss in obese mice by increasing energy expenditure rather than suppressing appetite. Published in Science Advances, the findings are notable because current injectable weight-loss drugs such as semaglutide often cause gastrointestinal side effects, muscle loss and rapid weight regain once treatment stops, so a compound that burns fat while sparing lean mass could address a major gap in obesity treatment.

TOFA reduced body weight in mice by an average of 18% without altering food intake or causing significant muscle loss, and treated mice burned up to 18% more energy without becoming less active or overheating. Combining TOFA with semaglutide or tirzepatide produced greater improvements in weight, blood sugar, insulin and triglycerides than either drug alone, and mice kept their weight down after stopping TOFA, unlike those previously given semaglutide. The compound also reduced liver fat, inflammation and scarring in mouse models of fatty liver disease, though experts caution obesity is complex, and the drug has so far only been tested in male mice, not in humans.