Weight Loss Discovery with Oral Compound in Mice

A research team from the University of California, Berkeley, uncovered a decades-old oral compound that led to significant weight loss in obese mice. Unlike typical methods that curtail appetite, this compound enhances energy expenditure. Published in Science Advances, the study noted that the molecule, called TOFA, decreased mice body weight by approximately 18%, maintaining consistent food intake without significant lean mass loss.

“Muscle mass is crucial for daily function. Preventing muscle loss during weight loss is a key challenge,” said Dr. Leslie Pristas, a bariatric surgeon.

Popular weight-loss medications like semaglutide focus on reducing food intake but often cause gastrointestinal side effects and loss of lean mass. Many patients regain weight after discontinuing these treatments. TOFA, instead of suppressing appetite, acts at the cellular level. It blocks enzymes involved in creating lipids, while boosting genes associated with fat burning. Mice on TOFA burned up to 18% more energy without becoming less active or experiencing harmful body heat increases.

The research found combining TOFA with obesity drugs like semaglutide or tirzepatide yielded better results in reducing weight and improving blood sugar levels. Mice treated with TOFA maintained stable weights post-treatment, unlike those on semaglutide who quickly regained weight.

“Obesity is complex. No single medication can entirely prevent post-treatment weight gain,” Pristas cautioned.

TOFA also showed promise in addressing metabolic dysfunction-associated steatohepatitis (MASH), a fatty liver disease, by reducing liver fat and inflammation without raising blood triglyceride levels.

Study Limitations

The study highlighted limitations, noting it only involved male mice. Further research is needed to assess if TOFA has similar effects on female mice. Human trials have yet to determine appropriate dosage, long-term safety, or potential side effects. Pristas emphasized the necessity of medical consultation for weight-related concerns.

Despite the promising results, the treatment must be carefully evaluated for hidden side effects. Researchers involved with the study have associations with ReRx Therapeutics, a company with the rights to develop the TOFA-related discovery.