A groundbreaking new study has revealed that depriving mice of the essential amino acid cysteine causes a profound and rapid loss of body weight—up to 30% in just one week. Published in Nature on May 21, the research demonstrates that eliminating cysteine throws core metabolic processes into disarray, forcing the body to rapidly burn fat stores to meet energy demands.
Led by scientists at NYU Grossman School of Medicine, the study involved genetically engineering mice to disable their cysteine production and then feeding them a cysteine-free diet. The result: a metabolic crisis that prevented cells from converting food into usable energy, triggered fat mobilization, and revealed new insights into how the body processes fuel.
At the center of this breakdown is a small molecule called coenzyme A (CoA), a critical player in over 100 metabolic reactions and essential to nearly 4% of all enzymes. When cysteine levels plummeted, CoA production collapsed, crippling the machinery cells use to generate adenosine triphosphate (ATP), the body’s energy currency. As sugar-derived intermediates like pyruvate and citrate were lost through urine instead of being used for energy, fat reserves were tapped aggressively to compensate.
This study marks one of the first detailed explorations of CoA dysfunction in adult organisms, a feat previously limited due to the early lethality of mice with impaired CoA production. It also offers an unprecedented look at the metabolic consequences of removing any of the nine essential amino acids—nutrients that the body cannot synthesize and must acquire from food.
The team found that cysteine depletion triggered two major cellular stress responses: the integrated stress response (ISR), which helps restore internal balance, and the oxidative stress response (OSR), which is activated by rising levels of reactive oxygen species (ROS) after the body’s glutathione reserves were exhausted. These stress signals—normally seen in cancer cells—worked together in healthy tissue to further disrupt metabolism. The result was increased production of the stress hormone GDF15, which suppresses appetite and inhibits fat creation, accelerating fat loss.
While the discovery opens new scientific avenues, researchers caution against seeing it as a direct pathway to weight-loss treatments. Cysteine is present in nearly all foods, making it virtually impossible to avoid in a normal diet. Any medical attempt to suppress cysteine could also carry serious health risks, as the amino acid plays a critical role in detoxification and organ protection.
Nonetheless, the study points to important nutritional implications. Plant-based diets rich in fruits, vegetables, and legumes typically have lower levels of cysteine and its precursor methionine (another sulfur-containing amino acid), compared to red meat. Previous research linked methionine restriction to health benefits, but this new work suggests cysteine may be the key factor. Understanding its role could help shape dietary recommendations or therapeutic strategies targeting specific aspects of metabolic health.
According to the researchers, future studies will use genetic techniques to selectively restore cysteine production in specific tissues to better understand which organs or systems drive the observed fat loss. The ultimate goal is to identify ways to safely manipulate these pathways in humans—potentially triggering similar metabolic changes without fully eliminating cysteine.
By stripping away one essential amino acid, this research has exposed the fragility and complexity of human metabolism—and offered a fresh perspective on how weight regulation and cellular energy management are tightly interconnected.
By Impact Lab
