Researchers investigated a compound, known as TOFA, which boosts energy expenditure without altering diet. In obese mice, TOFA raised the body's energy burning rate by up to 18%, with even greater effects observed when combined with medications such as Ozempic. The findings suggest an alternative ap…
Researchers investigated a compound, known as TOFA, which boosts energy expenditure without altering diet. In obese mice, TOFA raised the body's energy burning rate by up to 18%, with even greater effects observed when combined with medications such as Ozempic. The findings suggest an alternative approach to obesity treatment, distinct from current drugs that suppress appetite. Instead of reducing hunger, TOFA increases the body's energy expenditure, without affecting food intake in the animals. A study conducted by University of California at Berkeley researchers and published in Science Advances revealed this mechanism. TOFA was first synthesized in the 1970s and belongs to a class of ACC inhibitors, which block lipid production in the body. Several compounds in this class had reached intermediate clinical trial stages but were not approved for metabolic diseases due to side effects like increased triglyceride levels, associated with cardiovascular risk. According to the researchers, TOFA behaves differently, blocking lipid production while activating cellular receptors PPARα and PPARδ, which regulate genes involved in fat absorption and burning. In mice, this dual mechanism increased energy expenditure by up to 18%, without increased physical activity or body temperature. The team also tested TOFA at lower doses combined with semaglutide and tirzepatide, the active ingredients in Ozempic and Mounjaro. The combination produced greater improvements in weight loss, blood sugar control, insulin levels, and triglycerides than any treatment used alone. Näär described TOFA as working 'additively or synergistically' with appetite-suppressing medications, seeing it as complementary to GLP-1, not a replacement. In another experiment, mice treated with TOFA maintained weight loss for a longer period after treatment ended, while those receiving only semaglutide regained weight quickly upon returning to their previous diet. The researchers acknowledged limitations of their study: small group sizes, short duration, and male-only subjects, leaving open the question of effects in females. TOFA has never been tested in humans, its minimum effective dose is unknown, and it has not undergone necessary safety tests for medical use. Näär and two other authors are cofounders and shareholders of ReRx Therapeutics, a company developing TOFA as a potential treatment, which they declared as a conflict of interest in the scientific article. Future research includes toxicity and efficacy tests in rats and larger animals with physiology closer to humans, necessary before any human clinical trial can begin.
