Physical Exercise Reduces Appetite Through Lac-Phe Compound: New Study Findings

Researchers from Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Stanford University School of Medicine, and other institutions have discovered a new way exercise aids weight loss. Their study found that Lac-Phe, a compound produced during physical activity, reduces appetite in mice, leading to weight loss. These findings were published in Nature Metabolism.

"Regular exercise is considered a powerful way to lose weight and to protect from obesity-associated diseases, such as diabetes or heart conditions," said co-corresponding author Dr. Yang He, assistant professor of pediatrics–neurology at Baylor and investigator at the Duncan NRI. "Exercise helps lose weight by increasing the amount of energy the body uses; however, it is likely that other mechanisms are also involved."

Previous studies indicated that Lac-Phe levels rise significantly in the bloodstream after intense exercise. This pattern is seen not only in mice but also in humans and racehorses. The same research team had earlier shown that administering Lac-Phe to obese mice reduced their food intake and promoted weight loss without adverse effects. However, how Lac-Phe curbs appetite was unclear until now.

The researchers delved into two types of neurons in the mouse brain: AgRP neurons located in the arcuate nucleus of the hypothalamus, which trigger hunger; and PVH neurons in the paraventricular nucleus, which suppress hunger. Under typical conditions, AgRP neurons inhibit PVH neurons, creating hunger sensations.

The study revealed that Lac-Phe directly affects AgRP neurons by reducing their activity. This suppression allows PVH neurons to become more active, leading to decreased food consumption by mice. Notably, this reduction in appetite did not alter their overall behaviour, indicating no negative side effects from Lac-Phe.

Further investigation showed how Lac-Phe inhibits AgRP neurons. "We found that Lac-Phe acts on a protein on AgRP neurons called KATP channel, which helps regulate cell activity," He said. "When we blocked the KATP channels using drugs or genetic tools, Lac-Phe no longer suppressed appetite. This confirmed that the KATP channel is essential for Lac-Phe’s effects."

Implications for Human Weight Management

Although this research focused on mice, scientists believe these findings hold promise for human applications. Future studies will examine how Lac-Phe operates under various metabolic conditions like obesity and leanness. Researchers aim to understand its journey to the brain and explore its potential as a safe therapeutic option.

This discovery opens new avenues for understanding how exercise influences weight management beyond just calorie burning. By exploring these mechanisms further, scientists hope to develop innovative treatments for obesity-related issues.

With inputs from WAM