Experimental drug burns fat without suppressing appetite

Researchers at the University of California, Berkeley, found that the compound, known as TOFA, caused obese mice to lose an average of about 18% of their body weight over four weeks, without changes in food intake or physical activity. The findings were published in Science Advances.

TOFA, short for 5-tetradecyloxy-2-furoic acid, has been used in laboratory research since the 1970s. Its weight-loss effects appear to be linked to changes in how the body processes fat and uses energy.

Male obese mice were given TOFA twice daily for four weeks. Most of the weight they lost came from fat, while their muscle mass and lean tissue were largely preserved.

The mice did not eat less or become more active, and their body temperature did not increase. However, their energy expenditure rose by as much as 18%, suggesting that the compound prompted the body to use more energy without requiring dietary restriction or increased physical activity.

TOFA appears to work through two simultaneous pathways: reducing the production of new fat while helping cells absorb and burn fat for energy. However, the mechanism behind the full increase in energy expenditure remains unclear.

The treatment also produced metabolic benefits. Mice receiving TOFA showed lower levels of blood glucose, insulin and fat in the blood and liver, along with improved glucose tolerance and reduced markers of fatty liver disease.

The researchers also tested low doses of TOFA in combination with semaglutide and tirzepatide, two weight-loss drugs that primarily work by reducing appetite. The combined treatments produced greater weight loss and improved some metabolic measures compared with either treatment alone, suggesting that their mechanisms could complement each other.

In another experiment, mice treated with TOFA maintained their lower weight for longer after treatment stopped, while mice given semaglutide rapidly regained weight as their food intake increased.

The findings remain preliminary. The experiments involved a limited number of male mice, and TOFA has not yet been tested in humans. Its effectiveness, safety and appropriate dosage therefore remain unknown.

The researchers plan to conduct further toxicity and efficacy studies in larger animals before considering clinical trials in humans.