A research team led by scientists from the University of California, Berkeley, has identified a decades-old oral compound capable of producing significant weight loss in obese mice. Unlike many weight-loss medications that suppress appetite, this compound, known as TOFA, boosts energy expenditure. The study, published in Science Advances, highlights that TOFA led to an average reduction of 18% in body weight without altering the mice’s food intake or causing significant lean mass loss.
Preserving Muscle During Weight Loss
Unlike injectable medications like semaglutide, which can reduce food intake, TOFA focuses on energy expenditure. Semaglutide users sometimes experience gastrointestinal issues and loss of lean mass. Further, people often regain weight after stopping these treatments. Dr. Leslie Pristas, a bariatric surgeon, emphasized the importance of maintaining muscle mass during weight loss, as it aids day-to-day function and combats aging effects.
TOFA works by operating at the cellular level. It blocks enzymes crucial in lipid production while activating receptors that burn fat and produce energy. In experiments, treated mice burned up to 18% more energy without a decrease in activity or unsafe body temperature increases.
Combination With Existing Medications
The study examined combining TOFA with existing drugs like semaglutide and tirzepatide. This combination led to more significant reductions in body weight and improvements in blood sugar and other metabolic markers compared to using the drugs alone. Mice treated with TOFA kept stable weights post-treatment, unlike those who used semaglutide and regained weight quickly.
Patient Advice and Trial Limitations
Experts advise caution against assuming any one medication can permanently prevent post-treatment weight gain, noting the complexity of obesity causes, as mentioned by Dr. Pristas. She highlighted that abrupt cessation of medication might prompt the body to revert to its previous weight.
Additionally, TOFA showed potential in treating metabolic dysfunction-associated steatohepatitis (MASH) by reducing liver fat, inflammation, and fibrosis without raising triglyceride levels, a common issue with similar drugs.
Future Research and Safety Concerns
The study’s limitations include its focus on male mice. Researchers need to investigate the effects on female subjects. TOFA has not been tested on humans, so appropriate dosing and long-term safety remain unknown. Dr. Pristas cautioned that manipulation of the body’s lipid processes could lead to unforeseen side effects. Future treatments might combine TOFA with other therapies.
Some researchers of the study have disclosed connections to ReRx Therapeutics, a company interested in developing the TOFA-related discovery.