Many scientists and drug companies are trying to find ways to make the body behave as if it is cold, triggering thermogenesis without ice baths or freezing temperatures. But obesity researchers Philip Ruppert and Jan-Wilhelm Kornfeld from the Department of Biochemistry and Molecular Biology (BMB) at the University of Southern Denmark explored a different strategy.

Instead of lowering temperature, they investigated whether diet alone could switch on thermogenesis.

Their focus was on reducing two specific amino acids in food: methionine and cysteine.

After a series of experiments in mice, the team found that diet induced thermogenesis produced almost the same weight loss as constant exposure to five degrees Celsius around the clock. The study was conducted with BMB colleagues Aylin Güller, Marcus Rosendahl, and Natasa Stanic, and the results were published in the journal eLife.

Cutting Methionine and Cysteine Boosted Energy Burn

Over seven days, the researchers adjusted the levels of methionine and cysteine in the animals’ diets. Mice that ate a diet low in these amino acids burned more calories than mice fed a standard diet.

“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. They lost more weight, and it was not because they ate less or exercised more — they simply generated more heat,” explains Jan-Wilhelm Kornfeld.

Kornfeld is a molecular biologist and a professor with the Danish Diabetes and Endocrine Academy (DDEA) at the Novo Nordisk Foundation Center for Adipocyte Signaling at BMB, University of Southern Denmark.

Methionine and cysteine are found in high amounts in animal based proteins such as meat, eggs, and dairy. They are present in much lower amounts in plant foods like vegetables, nuts, and legumes that are associated with healthy aging (as shown in this study). Because vegetarians and vegans avoid animal products, they naturally consume less methionine and cysteine than people who regularly eat meat.

Beige Fat Activation and Calorie Burning

The researchers also wanted to know where the extra calorie burning occurred. They found that it took place in beige fat, a type of fat stored just under the skin in both mice and humans. This same fat tissue is activated during cold exposure.

Fat was burned in beige fat during both cold induced thermogenesis and diet induced thermogenesis.

“This tells us that beige fat doesn’t care whether the burning is triggered by cold or by diet,” says Philip Ruppert.

Ruppert, a molecular biologist with a PhD, was at SDU when the study was performed and is now at Cornell University in New York.

“We know from other studies that vegetarians and vegans are, in several respects, healthier than meat-eaters. We haven’t tested a methionine/cysteine-restricted diet in humans, only in mice, so we can’t say for certain that the same effect would occur in people — but it’s absolutely a possibility,” he says.

Potential New Obesity Treatments

The researchers believe the next step is to explore whether future obesity treatments could safely increase energy expenditure without requiring major lifestyle changes from patients.

They are also interested in developing functional foods that are naturally low in methionine and cysteine.

“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,” says Kornfeld.