New research reveals that reducing cysteine, an amino acid, can flip fat from storage mode to calorie-burning mode.
In both human trials and animal studies, lower cysteine levels sparked the transformation of white fat into heat-producing brown fat, resulting in weight loss, improved metabolism, and even reduced inflammation.
Calorie Restriction’s Hidden Amino Acid Link
Cutting calories is widely recognized as a way to improve health and shed excess weight, but new research in I highlights a more specific factor: the sulfur-containing amino acid cysteine. In the study titled “Cysteine depletion triggers adipose tissue thermogenesis and weight loss,” scientists found that when participants reduced their calorie intake, cysteine levels in white fat also dropped.
Researchers at Pennington Biomedical, including Dr. Eric Ravussin and Dr. Krisztian Stadler, explored cysteine’s role in fat metabolism and discovered that its reduction promotes the conversion of white fat cells into brown fat cells. Brown fat is more metabolically active, using energy to produce heat and maintain body temperature. In animal studies, completely removing cysteine led to substantial weight loss, increased fat burning, and enhanced browning of fat cells, underscoring cysteine’s influence on metabolic processes.
Beyond Calorie Counting: Redox and 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 findings draw on data from both human and animal trials. In the human study, fat tissue samples were collected from participants who had reduced calorie intake over a year. Researchers analyzed thousands of metabolites, compounds created as the body processes food and stores energy, and found a clear drop in cysteine levels.
“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.”
CALERIE Clinical Trial Findings
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.
A Potential Game-Changer for Obesity Treatment
“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: “Cysteine depletion triggers adipose tissue thermogenesis and weight loss” by Aileen H. Lee, Lucie Orliaguet, Yun-Hee Youm, Rae Maeda, Tamara Dlugos, Yuanjiu Lei, Daniel Coman, Irina Shchukina, Prabhakar Sairam Andhey, Steven R. Smith, Eric Ravussin, Krisztian Stadler, Bandy Chen, Maxim N. Artyomov, Fahmeed Hyder, Tamas L. Horvath, Marc Schneeberger, Yuki Sugiura and Vishwa Deep Dixit, 3 June 2025, Nature Metabolism.
DOI: 10.1038/s42255-025-01297-8
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7 Comments
Well, since cysteine is present in almost everything we eat, the best way to reduce cysteine intake is to stop eating . That does lead to rapid weight loss.
The problem is – cysteine can be produced in the body from methionine. How do we prevent that?
As a senior lay American male personally aware of connections between diet (food allergies/additives), dementia (family history) and obesity (borderline, sluggish metabolism) for more than four decades and not content to rely solely upon AI generated results, yesterday I followed-up the article with some extra searching. Already taking some of the recommended nutritional supplements, I still have some shopping to do to enhance my efforts to further improve my health/longevity, perhaps as easy now as 1-2-3: 1) Cysteine depletion triggers weight loss (https://www.nature.com/articles/s42255-025-01297-8), 2) MSG increases the level of cysteine (minimally; https://pubmed.ncbi.nlm.nih.gov/21030612/) and 3) Treatment (https://foodforthebrain.org/lowering-homocysteine-why-it-matters-and-how-to-do-it/). For me, based upon number “1),” number “2)” pretty well explains the global problems with dementia and obesity, minimally, and why added MSG should be permanently banned from all commercially prepared food products.
Reduction not total elimination.
“This resulted in a 40% drop in body temperature.”
So they killed the animal. Yes, that leads to weight loss.
40% drop in body temperature???
I can see how dropping one’s body temperature to below room temperature would lead to more than just brown fat cells. In fact, as decay sets in lots of things would turn darker.
Seriously, is 40% a typo?
From the reference, https://www.nature.com/articles/s42255-025-01297-8, there’s:
“In rodents, restriction of calories up to 40% reduces CBT and induces browning of the adipose
tissue of mice reared in sub-thermoneutral temperature”
To answer TheHeck’s question, apparently one reduces cysteine by starving oneself on a 60% calorie diet and shivering. If you’re willing to do that, your fat cells will turn brown. At least it’s known to happen in lab rats.
“With the reduction of cysteine, the participants also experienced subsequent weight loss, improved muscle health, and reduced inflammation.”
I realize that what I’m going to say is anecdotal but when most people I’ve known, including myself, stopped eating a significant percentage of calories and significant weight loss, we’ve also lost muscle. That’s a common outcome from a large calorie restriction. Was some type of weight training done and not mentioned in the article?