Deleting a single amino acid causes extreme weight loss in mice

Research published in the journal ' Nature ' has revealed that mice genetically modified to not produce cysteine, an amino acid found in protein-rich foods, lost nearly 30% of their body weight in just one week when fed a diet lacking the compound.

The discovery, made by scientists from the United States and Canada, could open new avenues for the development of obesity treatments, although their application in humans still poses significant challenges.

Stanford University researchers genetically modified mice to block the production of cysteine, an amino acid found in foods like wheat germ. The result was astonishing: the mice lost 30% of their body weight in one week.

The experiment showed that a lack of cysteine ​​reduces levels of glutathione (an antioxidant) and coenzyme A (key to metabolism), which triggers energy expenditure and fat loss, even without changes in diet.

Cysteine ​​is found naturally in foods such as meat, eggs, and whole grains .

In this study, researchers eliminated the enzyme cystathionine γ-lyase—key to cysteine ​​production—in mice using gene editing. They then compared their performance with that of normal mice fed ten different diets, each lacking an essential amino acid.

"Our findings suggest that many of the beneficial effects attributed to low-methionine diets are actually due to cysteine ​​depletion," explains Evgeny Nudler, a biochemist at New York University and co-author of the study.

Genetically edited mice on a cysteine-free diet lost 31% of their body weight . In contrast, mice that retained the enzyme did not experience this loss unless they were subjected to double restriction: cysteine ​​and calorie restriction, which also caused them to lose about 25% of their weight.

This discovery reinforces previous research suggesting metabolic benefits from diets low in amino acids such as methionine.

But new work now points to cysteine ​​as a key factor, which could redefine future dietary or pharmacological strategies.

Although the results in mice are promising, the extrapolation to humans is still uncertain. "Mice have a much greater capacity to generate body heat , which accelerates fat burning under calorie restriction," Nudler recalls.

Obesity, which affects more than 800 million people worldwide, represents an urgent challenge to global health.

However, the researchers clarify that it's not about eliminating cysteine ​​from the diet, but rather modulating how the body produces it.

However, a preliminary human clinical trial conducted at Pennsylvania State University showed that diets low in methionine and cysteine ​​were safe and promoted weight loss in overweight individuals. Still, the authors emphasize that larger, longer-term trials are needed to confirm the efficacy and safety of these interventions.

Cysteine ​​is essential for functions such as protein synthesis and cellular protection, so its alteration could be risky, as has been observed in studies on diseases such as Huntington's disease .

Reducing cysteine ​​intake through diet alone could be complicated, as this amino acid is present in most protein-rich foods. However, Nudler suggests that a low-cysteine ​​diet based on fruits and some vegetables could replicate some of the observed benefits.

Furthermore, the study opens the possibility of developing drug therapies that specifically reduce cysteine ​​levels in key organs such as the liver. "This could translate into more efficient fat loss without the need for such severe dietary restriction," the researchers write.