Researchers have developed a novel molecular compound that shows promise in tackling obesity and diabetes by boosting the body's fat-burning capabilities without causing muscle loss, a common side effect of current weight-loss medications.
While GLP-1 drugs like Ozempic and Wegovy have revolutionized weight management, they can lead to issues such as nausea and, crucially, muscle depletion. Scientists at UC Berkeley have taken a different route, focusing on increasing the body's energy expenditure rather than reducing calorie intake.
The compound, known as 5-tetradecyloxy-2-furoic acid (TOFA), works by inhibiting lipid production while simultaneously activating genes that encourage cells to burn fat for fuel. In studies with mice, TOFA improved insulin sensitivity, controlled glucose levels, reduced triglycerides, and reversed signs of fatty liver disease. Importantly, obese mice treated with TOFA lost fat mass without a significant decrease in lean muscle.
"Body weight responds to two levers: taking in fewer calories, or spending more energy," explained Anders Näär, a professor at UC Berkeley and senior author of the study published in Science Advances. "GLP-1s work almost entirely on the first, so we went after the second."
TOFA, a compound first discovered decades ago, belongs to a class called ACC inhibitors. Unlike some other ACC inhibitors that can raise triglyceride levels, TOFA also activates cellular receptors that enhance fat uptake and burning. This dual action appears to create a coordinated metabolic response, potentially explaining its effectiveness and lack of negative side effects in the mouse models.
Intriguingly, a combination of TOFA with existing GLP-1 medications in mice resulted in even greater improvements in weight, glucose control, and triglyceride levels than either treatment alone. Researchers view TOFA as a complementary therapy rather than a replacement for current options.
Despite these encouraging findings, TOFA has only been tested in animals. Its safety and efficacy in humans are yet to be determined and will require extensive future studies. To advance this research, the UC Berkeley team has launched a company called ReRx Therapeutics.
