Methionine Restriction May Boost Calorie Burning Without Cold Exposure

Cold conditions make the body use extra calories to maintain warmth. This inherent mechanism, known as thermogenesis, preserves body temperature by converting stored energy into heat.

Scientists have spent years looking for methods to stimulate this calorie-burning process without requiring people to endure freezing temperatures.

Researchers at the University of Southern Denmark investigated whether dietary changes alone might produce a comparable effect.

Rather than reducing the ambient temperature, they cut particular nutrients from the diet and closely tracked the body's response in controlled settings.

A diet that mimics cold

The team examined two amino acids: methionine and cysteine. These are widely found in animal-derived foods, including meat, eggs and dairy products.

Plant-based foods generally provide far smaller quantities of these amino acids. For the experiment, male mice were fed either a standard diet or a methionine-restricted diet.

While some groups were kept at room temperature, others were exposed to cold at 4°C.

This approach enabled the researchers to compare diet directly with cold exposure and assess whether food alone could meaningfully raise energy expenditure.

Energy burn without eating less

At room temperature, mice given the methionine-restricted diet used roughly 20% more energy than those fed the standard diet.

Food consumption was comparable between the groups, and activity levels remained unchanged. Their additional weight loss resulted from higher heat production rather than reduced eating or increased movement.

“The mice that burned the most energy ate the same amount of food as the others, and they didn’t move more or less. We saw a 20% increase in their thermogenesis,” noted Professor Jan Wilhelm Kornfeld.

“They lost more weight, and it was not because they ate less or exercised more – they simply generated more heat.”

A shift towards burning fat

The restricted diet altered the way the mice fuelled their bodies as well. They moved away from using carbohydrates and instead relied more heavily on fat for energy.

The scientists identified this change by measuring the respiratory exchange ratio, which indicates the fuel source favoured by the body. Introducing cold exposure caused energy expenditure to rise markedly in every group.

Cold was a strong stimulus, narrowing the observable differences between the diets. Nevertheless, the combination of cold and methionine restriction produced further weight loss and reduced blood triglyceride levels.

What happened inside the tissues

To explore the biological processes underlying the findings, the team analysed gene activity in multiple tissues: the liver, brown fat and two forms of white fat.

Brown fat is designed to generate heat, whereas white fat principally stores energy. In brown fat, cold exposure was the main driver of gene activity, with the restricted diet producing only a limited effect.

In the liver, cold chiefly switched genes on. By contrast, the combination of diet and cold frequently lowered the activity of certain genes associated with metabolism and energy processing.

Beige fat responded to both signals

The most pronounced combined effect was seen in inguinal white fat, which can take on the heat-producing characteristics of beige fat once activated. Within this tissue, methionine restriction and cold exposure worked additively.

Each intervention increased genes involved in fatty acid breakdown, PPAR signalling, thermogenesis and the TCA cycle, which contributes to energy production. The pattern indicates that diet alone can prompt a cold-like response in particular fat stores.

“This tells us that beige fat doesn’t care whether the burning is triggered by cold or by diet,” said Philip Ruppert, co-author of the study.

Hormones raise energy burn

Hormones were central to these effects. Restricting methionine increased FGF21, a hormone that tells the body to raise energy expenditure.

Cold exposure also increased FGF21 levels, although using both signals together did not elevate the hormone substantially further. This suggests the restricted diet already activates this pathway strongly.

Beta-hydroxybutyrate levels, which indicate fat burning in the liver, rose with either the diet or cold exposure, confirming that the intervention shifted the body towards greater fat use.

Why this matters for obesity

Nearly one billion adults around the world are affected by obesity, while many available treatments concentrate primarily on suppressing appetite.

GLP-1-based medicines such as semaglutide have reshaped weight-loss treatment, yet prolonged use may lower total energy expenditure. The researchers believe dietary strategies could potentially be combined with medication.

“It would also be interesting to study whether Wegovy patients experience additional weight loss if they switch to a diet without the amino acids methionine and cysteine – in other words, a diet free of animal proteins,” said Professor Kornfeld.

A new direction for weight control

The study was short-term and involved male mice only, meaning its results cannot yet be applied directly to humans.

Human physiology is more complicated, and longer-term research is required to determine whether people experience the same effects and whether they remain safe over time.

Even so, the results are encouraging. They suggest that adjusting specific dietary nutrients can activate the body's own heat-generating system and boost calorie burning without cold exposure.

Future weight-loss treatment could combine considered dietary changes with medicines, enabling the body to use more energy while appetite is also managed.