New research uncovers how the compound Lac-Phe, produced during intense exercise, suppresses appetite and aids in weight loss by targeting key brain neurons, paving the way for potential new weight management therapies.
Researchers from Baylor College of Medicine, Texas Children’s Hospital, Stanford University School of Medicine and other institutions have uncovered groundbreaking insights into the ways exercise aids in weight loss. A new study published in Nature Metabolism reveals that the compound Lac-Phe, produced during intense exercise, plays a crucial role in reducing appetite, thereby facilitating weight loss.
“Regular exercise is considered a powerful way to lose weight and to protect from obesity-associated diseases, such as diabetes or heart conditions,” co-corresponding author Yang He, an assistant professor of pediatrics – neurology at Baylor and investigator at the Duncan NRI, said in a news release. “Exercise helps lose weight by increasing the amount of energy the body uses; however, it is likely that other mechanisms are also involved.”
This new discovery builds on prior research that identified Lac-Phe as the most increased metabolite in the blood after rigorous exercise in mice, humans and racehorses. Previously, the research team showed that administering Lac-Phe to obese mice could curb their appetite and lead to weight loss without adverse effects.
Until now, however, the precise mechanism by which Lac-Phe functions was not fully understood.
“Understanding how Lac-Phe works is important for developing it or similar compounds into treatments that may help people lose weight,” He added. “We looked into the brain as it regulates appetite and feeding behaviors.”
The team focused on two types of brain cells in mice: AgRP neurons, which promote hunger, and PVH neurons, which help suppress appetite. Typically, AgRP neurons inhibit PVH neurons, making one feel hungry.
However, the study revealed that Lac-Phe directly inhibits AgRP neurons, which in turn activates PVH neurons and reduces appetite.
The absence of behavioral side effects in the mice suggests that Lac-Phe does not cause unpleasant reactions, further highlighting its potential as a therapeutic agent.
Further research showed that Lac-Phe inhibits AgRP neurons by acting on a protein called KATP channel, which is crucial in regulating cell activity.
“When Lac-Phe activates these channels in AgRP neurons, the cells become less active,” added He. “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.”
This study sheds light on how exercise can naturally curb appetite and boost metabolism.
“The results also suggest the exciting possibility of targeting this newly discovered mechanism for weight management,” added co-corresponding author Yong Xu, who is currently at the University of South Florida.
“This finding is important because it helps explain how a naturally produced molecule can influence appetite by interacting with a key brain region that regulates hunger and body weight,” added co-corresponding author Jonathan Long, an associate professor of pathology at Stanford University School of Medicine.
This promising research, although primarily conducted in mice, sets the stage for future studies to explore Lac-Phe’s effects in humans. Upcoming investigations will determine how the compound functions in different metabolic states, such as obesity versus leanness, and evaluate its safety and efficacy as a potential weight loss therapy.
Source: Baylor School of Medicine