Reduction in Amino Acid Cysteine Triggers Weight Loss

July 7, 2025 · Baton Rouge, LA

Pennington Biomedical researchers contribute to study on the key role of cysteine in metabolism 

 Consuming fewer calories is largely accepted as a way to improve health and lose weight, but a recently published study in Nature Metabolism points to a specific sulfur-containing amino acid cysteine as a key component in weight loss. In the study “Cysteine depletion triggers adipose tissue thermogenesis and weight loss,” researchers discovered that when study participants restricted their calorie intake, it resulted in reduced levels of cysteine in white fat.

 Pennington Biomedical researchers Dr. Eric Ravussin and Dr. Krisztian Stadler contributed to the study in which they and colleagues examined cysteine and discovered that it triggered the transition of white fat cells to brown fat cells, which are a more active form of fat cells that burn energy to produce heat and maintain body temperature. When researchers restricted cysteine in animal models entirely, it drove high levels of weight loss and increased fat burning and browning of fat cells, further demonstrating cysteine’s importance in metabolism. 

“In addition to the dramatic weight loss and increase in fat burning resulting from the removal of cysteine, the amino acid is also central to redox balance and redox pathways in biology,” said Dr. Stadler, who directs the Oxidative Stress and Disease laboratory at Pennington Biomedical. “These results suggest future weight management strategies that might not rely exclusively on reducing caloric intake.”

The article is based on results from trials involving both human participants and animal models. For the human trials, researchers examined fat tissue samples taken from trial participants who had actively restricted calorie intake over a year. When examining the fat tissue samples, they looked for changes in the thousands of metabolites, which are compounds formed when the body breaks down food and stores energy. The exploration of these metabolites indicated a reduced level of cysteine. 

“Reverse translation of a human caloric restriction trial identified a new player in energy metabolism,” said Dr. Ravussin, who holds the Douglas L. Gordon Chair in Diabetes and Metabolism at Pennington Biomedical and oversees its Human Translation Physiology Lab. “Systemic cysteine depletion in mice causes weight loss with increased fat utilization and browning of adipocytes.”

The tissue samples came from participants in the CALERIE clinical trial, which recruited healthy young and middle-aged men and women who were instructed to reduce their calorie intake by an average of 14% over two years. With the reduction of cysteine, the participants also experienced subsequent weight loss, improved muscle health, and reduced inflammation. 

In the animal models, researchers provided meals with reduced calories. This resulted in a 40% drop in body temperature, but regardless of the cellular stress, the animal models did not exhibit tissue damage, suggesting that protective systems may kick in when cysteine is low.

"Dr. Ravussin, Dr. Stadler, and their colleagues have made a remarkable discovery showing that cysteine regulates the transition from white to brown fat cells, opening new therapeutic avenues for treating obesity," said Dr. John Kirwan, Executive Director of Pennington Biomedical Research Center. "I would like to congratulate this research team on uncovering this important metabolic mechanism that could eventually transform how we approach weight management interventions."