promising new weight loss and diabetes treatment helps burn fat while keeping muscle

The University of California reports on UC Berkeley research into a potential treatment for obesity and diabetes that works differently from GLP-1 drugs such as Ozempic, Wegovy, Mounjaro, and Zepbound. Instead of primarily reducing appetite and food intake, the experimental compound, called TOFA, appears to increase energy expenditure by encouraging cells to burn fat. The work, published in *Science Advances*, was led by researchers in Professor Anders Naar’s lab at UC Berkeley, with Justin Y. Lee as first author. The article frames the study as an attempt to address some limitations of GLP-1 therapies, including gastrointestinal side effects, nutritional concerns, and possible lean muscle loss.

In mouse experiments, TOFA improved insulin sensitivity and glucose control, lowered triglycerides, and improved features of fatty liver disease. Obese mice lost fat without significant loss of lean muscle mass. Mechanistically, the researchers found that TOFA does more than block lipid production as an ACC inhibitor; it also activates PPAR-alpha and PPAR-delta pathways, which help cells take up and burn fat. The mice burned up to 18% more energy without increased physical activity or body temperature. The researchers also tested TOFA alongside GLP-1 drugs such as semaglutide and tirzepatide, finding greater improvements in weight, glucose control, insulin levels, and triglycerides than with either approach alone. The major caveat is that this remains animal research: TOFA has not yet been proven safe or effective in humans, and the article discloses that several researchers are connected to ReRx Therapeutics, a company formed to develop the related intellectual property.