UC Berkeley researchers develop compound that burns fat while preserving muscle in preclinical study

The past five years have belonged to a class of drugs that transformed how doctors treat obesity, diabetes, and fatty liver disease. Ozempic, Wegovy, Mounjaro, Zepbound—these GLP-1 medications work by making people feel full faster, suppressing appetite, and helping them eat less. They are effective. They have also made their manufacturers very rich. But they come with a cost that doesn't show up in the marketing materials: people taking them often experience nausea and gastrointestinal distress, and because the drugs work by reducing food intake, they can trigger nutritional deficiencies and muscle loss. Lose enough muscle and you become frail. Lose enough nutrients and your body begins to fail in ways that take years to fully understand.

At UC Berkeley, a team of researchers decided to chase a different metabolic lever entirely. Instead of making people eat less, what if you could make their bodies burn more? What if you could flip the switch on energy expenditure—the rate at which cells consume fuel—rather than the switch on appetite?

They found a compound called TOFA, or 5-tetradecyloxy-2-furoic acid, that does exactly that. In experiments published in Science Advances, the researchers showed that TOFA blocks the production of lipids like cholesterol and triglycerides while simultaneously activating genes that help cells burn fat and generate energy. In obese mice, the compound produced weight loss from fat tissue specifically, with no meaningful loss of lean muscle. The mice's insulin sensitivity improved. Their glucose control improved. Their triglyceride levels dropped. The features of fatty liver disease improved.

What makes TOFA unusual is its dual mechanism. It works as an ACC inhibitor—a class of compounds discovered in the 1970s that block lipid production—but it also activates two cellular receptors called PPARα and PPARδ, which turn on the genes that let cells consume fat as fuel. In the mice studied, this combination caused cells to burn up to 18 percent more energy without any increase in physical activity or body temperature. Other ACC inhibitors have a serious drawback: they raise triglycerides, which is bad for the heart. TOFA does not. When the researchers tried giving mice two separate compounds—one to block lipid production and another to boost energy expenditure—the combination was less effective than TOFA alone. The coordinated response matters.

Anders Näär, a professor of metabolic biology and nutrition at Berkeley and the study's senior author, framed the discovery in simple terms: "Body weight responds to two levers: taking in fewer calories, or spending more energy. GLP-1s work almost entirely on the first, so we went after the second." His team also tested whether TOFA could work alongside existing GLP-1 drugs. In mice, combining TOFA with semaglutide or tirzepatide produced greater improvements in body weight, glucose control, insulin levels, and triglycerides than either treatment alone. Näär emphasized that TOFA is not meant to replace GLP-1 medications but to complement them—a different tool for a different part of the problem.

The caveat is substantial: TOFA has been tested only in animals. No human has taken it. No one knows if it will be safe in people, or if the metabolic improvements seen in mice will translate to the human body. The researchers have founded a company called ReRx Therapeutics to move the work toward clinical trials. That journey from mouse to human, from laboratory finding to approved medication, typically takes years and costs hundreds of millions of dollars. It is not guaranteed to succeed. But for people struggling with obesity and diabetes, and for those who have experienced the muscle-wasting side effects of current treatments, the possibility of a drug that burns fat while preserving the body's structural integrity represents something worth watching.