Experimental Compound Burns Fat Without Muscle Loss in Mice

A molecular compound called 5-tetradecyloxy-2-furoic acid (TOFA) helped obese mice burn more energy and lose fat while preserving muscle mass. The compound also improved blood sugar levels, reduced triglycerides, and alleviated fatty liver disease in the mice. This research suggests a new strategy for treating obesity by increasing the body's energy expenditure rather than solely reducing appetite.

Current GLP-1 medications, such as Ozempic and Wegovy, primarily reduce appetite and food intake. While effective for weight loss, these drugs can lead to muscle loss and nutritional deficiencies. Researchers at the University of California, Berkeley, are exploring methods to increase metabolic activity instead.

TOFA, an ACC inhibitor first identified in the 1970s, interferes with lipid production. Unlike other ACC inhibitors, TOFA also activates PPARα and PPARδ. These cellular receptors switch on genes that promote fat utilization for fuel and increased energy production. In mouse studies, TOFA increased energy use by up to 18% without increasing physical activity or body temperature. It did not cause the rise in triglycerides observed with some other ACC inhibitors.

Combining TOFA with GLP-1 drugs like semaglutide and tirzepatide resulted in greater improvements. These improvements included body weight reduction, glucose control, insulin levels, and triglycerides. The researchers noted that TOFA appears to complement existing GLP-1 treatments. The compound's multi-functional action on both lipid synthesis and energy expenditure pathways may be key to its effectiveness.

Human testing is necessary to evaluate the safety and efficacy of TOFA. The researchers have formed ReRx Therapeutics to advance this compound toward clinical trials. This study was funded by discretionary funds from UC Berkeley, with additional support from the UCSF Liver Center and the University of Michigan Animal Phenotyping Core.