Weight loss: Appetite-suppressing molecule helps obese mice slim down

Lac-Phe, an altered form of an amino acid produced by mice and humans after exercise, can help obese mice lose weight by suppressing their appetite

By Carissa Wong

An altered form of an amino acid that is produced in both humans and mice after exercise can be used to help mice that are obese lose weight by suppressing their appetite. The findings could eventually lead to a new form of drug for treating obesity.

Until now, the biological role of the molecule lac-phe, which is produced when the amino acid phenylalanine reacts with another molecule called lactate, has been unclear.

Yong Xu at the Baylor College of Medicine, Texas, and his colleagues have now found evidence that lac-phe reduces the appetite of mice after exercise.

“We found this metabolite called lac-phe can rapidly increase in the circulation after exercise, not only in mice, but also in humans,” says Xu. “We also found this metabolite can be administered to suppress food intake and decrease body weight in an obese mouse model.”

Xu and his colleagues analysed the blood of five mice that had run to exhaustion on a treadmill and found that the concentration of lac-phe increased more than that of any other molecules produced as a result of the exercise.

They then injected 12 mice that were obese with either lac-phe or a control saline solution every day for 10 days. The team found that the mice given lac-phe consumed half as much food as the control mice within the 12 hours following the first injection, leading to a significant loss of nearly 3 grams in body weight by day eight. The researchers also gave lean mice lac-phe and found that the animals’ food intake was unaffected, suggesting the molecule only suppressed appetite in mice that were obese.

“My favourite theory is that during obesity, we know the blood-brain barrier may have increased permeability to lac-phe and other signals from the circulation, which means lac-phe may have better access to the brain to suppress food intake in only obese mice, but not lean mice. We are currently investigating this,” says Xu.

The team also found that lac-phe injections didn’t change the activity levels of the mice that were obese, and there was no evidence it reduced their appetite simply by making the animals nauseous and less interested in food.

By recruiting people to carry out sprint, resistance or endurance training, the researchers found that lac-phe levels also increase after exercise in humans – but the effect on appetite in humans needs to be confirmed.

“This could lead to the development of a pill that can directly be used to suppress appetite for certain individuals who cannot easily exercise because of other conditions, ageing or bone issues,” says Xu. “We just filed a patent for hopefully using this knowledge to treat human diseases such as obesity.”

“The work provides novel insight into the mechanisms by which exercise alters appetite and food intake in mice – findings that warrant further investigation and verification in humans,” says Hashim Islam at the University of British Columbia, Canada. “If indeed proven to be a potent regulator of appetite and food intake in humans, lac-phe may hold genuine therapeutic potential for combating obesity and cardiometabolic disease.”

Journal reference: Nature, DOI: https://doi.org/10.1038/s41586-022-04828-5