Scientists find one fat-burning amino acid that made mice lose 30% of their weight in a week; humans show promising metabolic effects

Obesity and related metabolic diseases are among the biggest health challenges of our time, affecting millions of people worldwide and driving up risks of diabetes, heart disease, and reduced lifespan.

While exercise and dieting are the most common interventions, scientists have been looking for biological pathways that might make weight loss more effective and sustainable.

A new study led by Aileen H. Lee from Yale School of Medicine, published in Nature Metabolism on June 3, suggests that one amino acid, cysteine, could hold the key.

Researchers found that removing cysteine from the diet triggers the body to switch from storing fat to burning it.

This discovery observed that rapid weight loss reprogrammed fat tissue into a calorie-burning state.

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The problem: How diet shapes longevity and fat metabolism

While it was clear that CR and MR triggered this browning effect, the exact amino acid responsible for sparking the transformation remained a mystery until recent research began pointing to cysteine as a central player in driving these health-promoting changes.

The research suggests that the benefits of caloric restriction (reducing overall calorie intake) or methionine restriction (limiting the essential amino acid methionine found in protein-rich foods) may not come only from eating less overall, but from specifically lowering certain amino acids like cysteine.

This could mean that a controlled diet helps with weight loss and metabolic health partly because it reduces cysteine intake, which then promotes the “browning” of fat.

So while counting calories alone works to some extent, it may not fully capture the biological effects that come from tweaking what kind of calories (or proteins) you eat.

In other words, the quality and composition of nutrients might matter as much, or more than the calorie number itself.

The discovery: Cysteine levels drop with caloric restriction

To test this hypothesis, the researchers conducted an experiment using mice that were unable to synthesize their own cysteine.

Compared to mice capable of making the amino acid, mice without cysteine in their diets saw a dramatic 25-30 percent drop in body weight in a single week.

While the study didn’t involve human test subjects, the researchers did look at data from 238 adults who had previously enrolled in a calorie-reduction diet experiment.

Data indicated that these individuals had lower levels of cysteine in their fat tissue, suggesting a possible link between calorie intake and cysteine levels in people.

So, can blocking cysteine altogether help in weight loss?

Not really, as researchers suggest that cysteine could become a target for carefully tuning the body’s metabolism, but the approach demands caution.

In studies, blocking cysteine led to a dangerous drop in body weight in mice, although this was reversed once cysteine was restored.

Since the amino acid also plays vital roles in other metabolic processes, any attempt to restrict it must be approached with great care.

This way it connects the idea of “metabolic hacking” with the risks and biological necessity of cysteine, so readers don’t walk away thinking cutting it out is safe.

Could similar metabolic rewiring benefit humans?

In mice, cutting out cysteine caused fat to “brown,” turning it into a calorie-burning form and leading to rapid weight loss, as much as 30 per cent of their body weight in just a week.

In humans, eating fewer calories also reprograms fat to burn more energy, but people don’t seem to use the same fat-burning protein (called UCP1) that mice do.

Instead, our bodies likely rely on other backup pathways to achieve similar benefits, showing that humans and mice may reach the same result but by different routes.

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