By eliminating the essential amino acid cysteine from the diets of mice, and disabling their ability to produce it, scientists have induced rapid and dramatic weight loss. The technique opens a new pathway to explore in weight-loss science.
In carrying out the study, researchers at New York University looked at the effects of eliminating a series of amino acids from the diets of mice, as well as genetically altering them to be unable to produce the compounds. Of all the aminos tested, knocking out cysteine led to rapid and drastic weight loss, reducing some of the rodents' body weights by 30% in just seven days.
The reason for the result was that when the cysteine was blocked, there was a corresponding drop in a small molecule called coenzyme A (CoA), which is found in all living things and is responsible for metabolic processes, including metabolizing fatty acids. When the levels of CoA dropped, there was a disruption in oxidative phosphorylation, a process that produces adenosine triphosphate (ATP), a molecule that stores and releases energy in the body.
Disrupting that process meant that the mice could no longer get energy from carbohydrates and instead turned to their own stored fat for energy. Furthermore, cysteine depletion also caused the increased production of a stress hormone known as GDF15, which contributes to food aversion. So, the mice not only cannibalized their own fat stores to get fuel which created the drastic weight loss, but they kept off the weight because they simply lost their appetites.
“Our surprising findings reveal that low cysteine levels triggered rapid fat loss in our study mice by activating a network of interconnected biological pathways,” said co-senior study author Evgeny Nudler. “While driving weight loss in the clinic remains a key future mission, we are most excited for the moment about the profound, fundamental aspects of metabolism revealed in this study.”
That being said, the researchers point out that eliminating cysteine from human diets is all but impossible because the amino acid is found in nearly all foods. Knocking out its production genetically would also pose serious health risks, as it is involved in critical biological functions including the protection of organs from toxins and medications.
Instead, the scientists say that their findings open a new way to think about and study weight loss. For example, they can now use genetic engineering to turn cysteine production back on selectively, to see how it affects overall weight loss. Doing so could lead to the development of techniques for restricting the amino acid in humans, to help them shed pounds.
“Given that achieving maximum cysteine deprivation weight loss in the mice was dependent on both diet and deletion of the gene, moving forward we can now restore cysteine production genetically in specific cells or tissues and determine the role of each in the dramatic weight loss we observed,” said co-senior author Dan L. Littman. “We hope in the future to hijack parts of this process to induce a similar weight loss in humans but without completely removing cysteine.”
The study has been published in the journal, Nature.
Source: NYU Langone Health