Cutting Cysteine May Activate Fat Loss Pathways: Study Finds

A study published in Nature Metabolism has revealed that a specific sulfur-containing amino acid, cysteine, plays a crucial role in weight loss and fat metabolism. Conducted by researchers including Dr. Eric Ravussin and Dr. Krisztian Stadler from Pennington Biomedical Research Center, the highlights a novel approach to obesity treatment.

Cysteine, an amino acid known for its role in redox balance and cellular metabolism, was found to drop significantly in participants who practiced long-term calorie restriction. This reduction was closely linked to the transformation of white fat cells into brown fat cells a more metabolically active type that burns energy to generate heat.

To understand this relationship, researchers studied both human participants and animal models. Human fat tissue samples were collected from participants in the CALERIE clinical trial, which involved healthy young and middle-aged adults reducing their caloric intake by an average of 14% over two years. Through extensive metabolic profiling, scientists observed that lowered cysteine levels were associated with weight loss, reduced inflammation, and improved muscle health.

Animal studies reinforced these findings. When cysteine was restricted entirely, animals showed marked weight loss, increased fat burning, and significant browning of white fat. Despite a 40% drop in body temperature, a sign of cellular stress there was no observed tissue damage. “Systemic cysteine depletion in mice causes weight loss with increased fat utilization and browning of adipocytes,” said Dr. Ravussin.

Dr. Stadler added, “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.”

With its dual benefits on fat metabolism and inflammation, cysteine depletion could represent a future cornerstone in combating obesity.

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