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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.” 

Reference: Lee AH, Orliaguet L, Youm YH, et al. Cysteine depletion triggers adipose tissue thermogenesis and weight loss. Nat Metab. 2025;7(6):1204-1222. doi: 10.1038/s42255-025-01297-8

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The skeletal muscles of men and women process glucose and fats in different ways. A study conducted by the University Hospital of Tübingen, the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich and the German Center for Diabetes Research (DZD) e.V. provides the first comprehensive molecular analysis of these differences. The results possibly give an explanation why metabolic diseases such as diabetes manifest differently in women and men – and why they respond differently to physical activity.

Skeletal muscles are far more than just “movement driving motors.” They play a central role in glucose metabolism and therefore also in the development of type 2 diabetes. This is due to the fact that around 85 percent of insulin-dependent glucose uptake takes place in the muscles. This means that if muscle cells react less sensitively to insulin, for example in the case of insulin resistance, glucose is less easily absorbed from the blood. This process is specifically counteracted by physical activity. 

Women’s and Men’s Muscles Work Differently

The degree to which muscles work differently in women and men has long been underestimated. It is precisely this issue which has now been investigated by researchers led by Simon Dreher and Cora Weigert. They examined muscle biopsies from 25 healthy but overweight adults (16 women, 9 men) aged around 30 years. The test subjects had not taken part in regular sporting activities beforehand. Over a period of eight weeks, they completed one hour of endurance training three times a week, consisting of 30 minutes of cycling and 30 minutes of walking on the treadmill.

Muscle samples were taken before they started, after they had the first training session and at the end of the program. Using state-of-the-art molecular biological methods, including epigenome, transcriptome and proteome analyses, the team investigated sex-specific differences at various levels. 

Men React with more Stress to Exercise 

The result: The first training session triggered a stronger stress response at the molecular level in men, which became manifest in the increased activation of stress genes and the increase in the muscle protein myoglobin in the blood. In addition, male muscles showed a distinct pattern of what are called fast-twitch fibers, which are designed for short-term, intensive exercise and preferably use glucose as an energy source.

Women had significantly higher amounts of proteins that are responsible for the absorption and storage of fatty acids: an indication of more efficient fat utilization. After eight weeks of regular endurance training, the muscles of both sexes matched and the muscle fiber-specific differences decreased. At the same time, women and men produced more proteins that promote the utilization of glucose and fat in the mitochondria, the “power plants of the cells.”

“These adjustments indicate an overall improvement in metabolic performance, which can help to reduce the risk of type 2 diabetes,” says Weigert. “In future, our new findings might help to better predict individual diabetes risks and tailor recommendations for exercise therapies more specifically to women and men.”

What happens next? The scientists now want to investigate the role sex hormones such as estrogen and testosterone play in these differences – and how hormonal changes in old age influence the risk of metabolic diseases. 

Reference: Dreher SI, Goj T, von Toerne C, et al. Sex differences in resting skeletal muscle and the acute and long-term response to endurance exercise in individuals with overweight and obesity. Molecular Metabolism. 2025;98:102185. doi:10.1016/j.molmet.2025.102185

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.