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

Fact checked by Nick Blackmer

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 medication metformin. 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.

Metformin is an oral diabetes medication that helps lower blood sugar levels by decreasing the amount of glucose absorbed from food. It is not approved as a weight-loss drug, but some people experience mild weight loss ranging from 3 to 6 pounds when taking the medication, according to Andres Splenser, MD, an endocrinologist at Memorial Hermann in Houston who was not involved in the study.

“The new study sheds some light into the mechanism by which metformin may lead to weight loss and may lead to newer agents that could target Lac-Phe and lead to other agents for the treatment of obesity,” he told Verywell in an email. “Although the study is promising, it is important to realize that appetite control is a complex system with many redundant pathways.”

Related: 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.

GLP-1 weight management drugs like Wegovy (semaglutide) work by targeting GLP-1 receptors in the brain that help you feel full. Researchers believe there is a gut-brain communication pathway influenced by Lac-Phe, but identifying specific receptors could help researchers develop new weight loss medications.

Related: 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 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.

Read the original article on Verywell Health.