A molecule already known to laboratories has produced a surprising result in obese animals: less fat, without loss of muscle mass.
Researchers studied TOFA, a small molecule that can be administered orally. They tested it on several animal models of obesity, including mice fed a high-fat diet. Unlike several current treatments, its action does not rely on reducing appetite. The animals therefore continued to eat, but their bodies expended more energy.
A significant proportion of the population is now obese.
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To understand this result, we need to look at what the body does with fat. It can produce and store it, but it can also use it as fuel. TOFA acts on several mechanisms involved in this balance. In particular, it reduces the activity of two enzymes involved in fat production and activates pathways that promote its use.
In the animals studied, this change in metabolism was accompanied by a reduction in obesity. The researchers also observed better glucose regulation and improvements in the accumulation of fat in the liver. Most importantly, muscle mass did not decrease, and the amount of food consumed was not reduced.
This point is attracting attention because weight loss does not solely correspond to the disappearance of fat. Some treatments or diets can also cause a decrease in lean mass, which includes muscle. An approach capable of promoting fat loss while preserving muscle could therefore be of particular interest, if this effect is eventually confirmed in humans.
The team also combined TOFA with semaglutide or tirzepatide, two molecules used to treat obesity and diabetes. These drugs act in particular by reducing food intake. In animals, combining them with TOFA produced effects superior to those obtained with each treatment separately on several parameters, including weight and insulin response.
The two approaches therefore do not act in the same way. Semaglutide and tirzepatide influence appetite in particular, whereas TOFA mainly changes how the body produces and expends its energy reserves. The authors therefore envision combining mechanisms rather than replacing existing medications.
These results nevertheless remain entirely preclinical. TOFA has not yet been tested as a treatment for obesity in humans, so this study cannot establish its safety or the appropriate dose. Before any clinical trial, the researchers will need to determine in particular whether the effects observed in animals can be achieved without toxicity in humans.