New Delhi: The Ozempic era has made appetite suppression the most talked-about route to weight loss. But these drugs can come with nausea and other gastrointestinal side effects, while reduced food intake can also contribute to nutritional deficiencies and muscle loss. Now, scientists are exploring a new way to shed fat pharmaceutically—by getting the body to burn more energy.
Researchers at the University of California, Berkeley, found that a compound called 5-tetradecyloxy-2-furoic acid, or TOFA, helped obese mice burn more energy, lose fat while preserving lean muscle, and improve several markers of metabolic health, including insulin sensitivity, glucose control, triglyceride levels and fatty liver disease.
The findings, published in Science Advances, point to a potentially different approach to treating metabolic disorders such as obesity, diabetes and fatty liver disease. While GLP-1 drugs such as Ozempic, Mounjaro, Zepbound and Wegovy work largely by suppressing appetite and reducing food intake, TOFA appears to target the other side of the equation by increasing energy expenditure.
“Body weight responds to two levers: taking in fewer calories, or spending more energy,” said Anders Näär, the UC Berkeley metabolic biology professor who led the study. “GLP-1s work almost entirely on the first, so we went after the second.”
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What is TOFA?
TOFA is not a new molecule. It was first described in the 1970s as an inhibitor of acetyl-CoA carboxylase (ACC), an enzyme involved in making fat.
Other ACC inhibitors have run into problems in drug development, including increases in triglycerides that could raise heart-health risks, but the Berkeley researchers found that TOFA may behave differently. In addition to blocking fat production, it activates cellular receptors involved in switching on genes that help cells take up fat and burn it for energy. In treated mice, energy expenditure increased by up to 18 per cent, without the animals becoming more active or developing a higher body temperature.
The result was a broader improvement in metabolic health. The obese mice lost fat while retaining lean muscle, and also showed lower triglycerides, less fat in the liver and improved glucose control.
The researchers then combined TOFA with GLP-1 drugs. In mice, the combination produced greater improvements in weight, glucose and triglycerides than either treatment alone, suggesting that increasing energy expenditure could eventually complement appetite-suppressing drugs.
But that possibility is still a long way from becoming a treatment for people. TOFA has not yet been tested for safety or effectiveness in humans.