Researchers at the University of California, Berkeley, have identified a compound that increases cellular energy expenditure, leading to weight loss in mice without suppressing appetite. This compound, known as 5-tetradecyloxy-2-furoic acid (TOFA), works by increasing metabolism, a mechanism distinct from current popular weight-loss drugs like Ozempic and Wegovy, which primarily reduce appetite.
In a study published in Science Advances, obese mice treated with TOFA experienced an 18 percent reduction in body weight over four weeks. Crucially, this weight loss was almost entirely from fat, with no significant changes in food intake or physical activity observed. This contrasts with GLP-1 receptor agonists, where a portion of weight loss can be attributed to muscle mass.
Dr. Anders Näär, a metabolism researcher and senior author of the study, explained that while GLP-1s affect calorie intake, TOFA targets energy expenditure. "Body weight responds to two levers: taking in fewer calories, or spending more energy," Näär stated. "GLP-1s work almost entirely on the first, so we went after the second."
TOFA was first identified in the 1970s and was previously investigated for metabolic diseases. However, development was halted due to concerns about elevated triglyceride levels, a risk factor for heart disease and stroke. The recent study noted that the compound did not raise triglyceride levels or body temperature in the mice, and did not find evidence of vomiting, though the research is still in its early stages.
Scientists administered TOFA orally to obese mice twice daily for four weeks. Analysis indicated that the compound prompted cells to consume more fat and burn up to 18 percent more energy than usual. The study also observed improved insulin sensitivity and blood sugar control in the treated mice. Researchers believe that maintaining food intake helped preserve muscle mass and avoid nutritional deficiencies, a potential advantage over appetite-suppressing drugs.
In a comparative part of the study, a group of obese mice received both TOFA and GLP-1s, demonstrating greater weight loss and metabolic improvements than those treated with either compound alone. This combined approach was attributed to both increased energy expenditure and reduced food intake.
The research team plans further investigation into TOFA's potential for human use. Näär, along with two other co-authors, has co-founded ReRx Therapeutics to develop TOFA, a process that is expected to take several years.