An 'Anti-Hunger' Molecule Produced After Exercise Could Help Develop New Weight Loss Drugs

Key TakeawaysLevels of Lac-Phe, an anti-hunger molecule, increase after taking the diabetes drug metformin.The same molecule increases after intense exercise and helps regulate weight loss.More research on Lac-Phe could lead to the development of new weight loss drugs.

Key Takeaways

Levels of Lac-Phe, an anti-hunger molecule, increase after taking the diabetes drug metformin.The same molecule increases after intense exercise and helps regulate weight loss.More research on Lac-Phe could lead to the development of new weight loss drugs.

Researchers are one small step closer to developing a new class of weight loss drugs.

A new study found elevated levels of Lac-Phe (N-lactoyl-phenylalanine), an “anti-hunger molecule,” in people and mice given the diabetes medicationmetformin.This finding could help explain metformin-induced weight loss and allow scientists to create new Lac-Phe targeting weight management medications.

Lac-Phe is naturally produced after intense exercise and suppresses appetite and food intake, which leads to weight loss.

“Exercise and metformin both have multiple different beneficial effects, and weight loss is one of them. We’re glad to see that Lac-Phe is a shared common downstream signaling molecule,”Shuke Xiao, PhD, a postdoctoral researcher at Stanford University and first author of the study, told Verywell.

Stanford Medicine researchers first discovered Lac-Phe in 2022 while studying exercise and metabolism-related molecules. Lac-Phe levels increased in mice, racehorses, and humans after exercise. When researchers blocked Lac-Phe production in some mice, they ate more than the mice with normal Lac-Phe production, leading scientists to believe this molecule helps regulate post-exercise appetite.

For the new study, researchers looked at blood samples from mice and humans and found higher Lac-Phe levels in the subjects using metformin compared to subjects not taking the drug.

Is Weight Loss a Side Effect of Metformin?

What Does this Mean for Weight Loss Drug Development?

Researchers still need to learn exactly how Lac-Phe works in the body to understand how to leverage this molecule as an appetite suppressant.

“We’re looking for the cellular targets of Lac-Phe on those appetite control neurons. And I think we are making good progress,” Xiao said.

Could GLP-1 Drugs Reduce Obesity-Related Cancers in the Future?

“Semaglutide works pretty well to reduce body weight,” Xiao said. “Some people are resistant and don’t really lose body weight in response to that. That means we still need to discover better drugs or a combination of multiple drugs with different targets in your body to better control the energy balance.”

Researchers discovered the GLP-1 hormone in the 1980s, but it took decades to develop semaglutide and tirzepatide for weight management.Scientists only discovered Lac-Phe two years ago, so more research is needed before weight loss drugs targeting Lac-Phe hit the market.

“Hunger is a primal instinct needed for survival, and many promising weight loss treatments that mechanistically made sense did not result in clinically significant weight loss in clinical trials,” Splenser said. “However, the more ways we can learn to target hunger and weight loss will give us more flexibility with future therapies.”

What This Means For YouA better understanding of how Lac-Phe suppresses appetite may help researchers create new weight-loss drugs in the future. Right now, it seems the diabetes drug metformin can boost Lac-Phe production. But metformin can cause a serious condition called lactic acidosis. While this is rare, it is important to talk to your healthcare provider about your risks before taking this medication.

What This Means For You

A better understanding of how Lac-Phe suppresses appetite may help researchers create new weight-loss drugs in the future. Right now, it seems the diabetes drug metformin can boost Lac-Phe production. But metformin can cause a serious condition called lactic acidosis. While this is rare, it is important to talk to your healthcare provider about your risks before taking this medication.

4 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Xiao S, Li VL, Lyu X, et al.Lac-Phe mediates the effects of metformin on food intake and body weight.Nat Metab. 2024. doi:10.1038/s42255-024-00999-9Li VL, He Y, Contrepois K, et al.An exercise-inducible metabolite that suppresses feeding and obesity.Nature. 2022;606(7915):785-790. doi:10.1038/s41586-022-04828-5MedlinePlus.Metformin.Sheahan KH, Wahlberg EA, Gilbert MP.An overview of GLP-1 agonists and recent cardiovascular outcomes trials.Postgrad Med J. 2020;96(1133):156-161. doi:10.1136/postgradmedj-2019-137186

4 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Xiao S, Li VL, Lyu X, et al.Lac-Phe mediates the effects of metformin on food intake and body weight.Nat Metab. 2024. doi:10.1038/s42255-024-00999-9Li VL, He Y, Contrepois K, et al.An exercise-inducible metabolite that suppresses feeding and obesity.Nature. 2022;606(7915):785-790. doi:10.1038/s41586-022-04828-5MedlinePlus.Metformin.Sheahan KH, Wahlberg EA, Gilbert MP.An overview of GLP-1 agonists and recent cardiovascular outcomes trials.Postgrad Med J. 2020;96(1133):156-161. doi:10.1136/postgradmedj-2019-137186

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Xiao S, Li VL, Lyu X, et al.Lac-Phe mediates the effects of metformin on food intake and body weight.Nat Metab. 2024. doi:10.1038/s42255-024-00999-9Li VL, He Y, Contrepois K, et al.An exercise-inducible metabolite that suppresses feeding and obesity.Nature. 2022;606(7915):785-790. doi:10.1038/s41586-022-04828-5MedlinePlus.Metformin.Sheahan KH, Wahlberg EA, Gilbert MP.An overview of GLP-1 agonists and recent cardiovascular outcomes trials.Postgrad Med J. 2020;96(1133):156-161. doi:10.1136/postgradmedj-2019-137186

Xiao S, Li VL, Lyu X, et al.Lac-Phe mediates the effects of metformin on food intake and body weight.Nat Metab. 2024. doi:10.1038/s42255-024-00999-9

Li VL, He Y, Contrepois K, et al.An exercise-inducible metabolite that suppresses feeding and obesity.Nature. 2022;606(7915):785-790. doi:10.1038/s41586-022-04828-5

MedlinePlus.Metformin.

Sheahan KH, Wahlberg EA, Gilbert MP.An overview of GLP-1 agonists and recent cardiovascular outcomes trials.Postgrad Med J. 2020;96(1133):156-161. doi:10.1136/postgradmedj-2019-137186

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