A research team led by scientists at the University of California, Berkeley, has identified a decades old oral compound that produced substantial weight loss in obese mice. The experimental molecule, known as TOFA, worked without suppressing how much the animals ate.

According to the study, published in Science Advances, TOFA appears to increase energy expenditure rather than primarily targeting appetite. The molecule reduced the body weight of the mice by an average of 18% without changing their food intake or causing a statistically significant loss of lean mass.

The findings could point toward a different approach from popular injectable weight loss medications such as semaglutide. Those drugs can produce substantial weight loss partly by reducing food intake, although some patients experience gastrointestinal side effects and loss of lean mass.

Studies have also found that people often regain a significant amount of weight after stopping treatment. Meanwhile, preserving muscle during weight loss remains one of the greatest clinical hurdles in obesity medicine, according to experts.

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Dr. Leslie Pristas, a bariatric surgeon and owner of Best Life Bariatrics and Medical Weight Loss in Northeast Ohio, stressed the importance of protecting muscle. She told Fox News Digital that muscle supports everyday function and helps fight the effects of aging.

"Building muscle is really hard. It takes a really long time. So if we can avoid having muscle loss while we're having weight loss, that's going to be so much better."

Rather than mainly affecting appetite, TOFA acts inside cells, according to the researchers. It blocks enzymes involved in producing lipids, including fats such as triglycerides, while activating cellular receptors that switch on genes involved in fat burning and energy production.

The treated mice burned up to 18% more energy under room temperature and mildly warm conditions. They did so without becoming less active or developing a dangerous increase in body temperature.

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Researchers also combined TOFA with existing obesity drugs, including semaglutide and tirzepatide. Those combination treatments produced greater body weight reductions and improvements in blood sugar, insulin and triglyceride levels than either drug alone.

After treatment ended, mice that received TOFA maintained body weights close to control levels. In contrast, mice that had previously received semaglutide began rapidly regaining weight.

However, Pristas cautioned against assuming that one medication could permanently prevent weight regain after treatment. "Obesity is super complex," she said. "There's not just one mechanism by which everyone gains weight or even a single person gains weight. There are a lot of overlapping factors."

She noted that extra body weight can become the level the body regards as its weight set point. If medication is stopped abruptly, she said, the body may then work to return to its previous weight.

TOFA also showed promise in mouse models of metabolic dysfunction associated steatohepatitis, known as MASH, which is a form of fatty liver disease. Mice given the compound had less liver fat, inflammation and fibrosis, or scarring.

The compound produced those liver benefits without raising triglyceride levels in the blood, the researchers noted. Some similar metabolic drugs have increased triglycerides, creating potential cardiovascular and other health concerns that complicated their development.

Still, the research remains at an early stage, and all the animal experiments involved male mice. Future studies will need to determine whether TOFA produces similar results in female animals.

TOFA has not been tested in people, leaving major questions unanswered. Researchers do not yet know what dose would be appropriate, whether prolonged use would be safe, or whether the compound could cause subtle toxicities or other safety problems.

Pristas said early mouse findings must be considered carefully because humans could experience hidden side effects. "If it sounds too good to be true, it's probably too good to be true," she said.

"When you're talking about manipulating our bodies' manufacturing or processing of lipids, it's complex. And so there can be downstream effects that we don't want. That's where we can't get too excited."

Even with those concerns, Pristas said the treatment could eventually benefit people, either by itself or in combination with another therapy. Patients concerned about their weight loss journey should speak with a professional before changing any medication.

The study authors disclosed that several researchers are cofounders, officers or equity holders in ReRx Therapeutics. The company has an agreement that gives it the option to develop the TOFA related discovery from the University of California, Berkeley.