The Benefits of Exercise in a Pill? Science Is Closer to That Goal

Overview: Researchers have identified a molecule in the blood that is produced during exercise. The molecule, Lac-Phe, can effectively reduce food intake and obesity in mouse models.

Source: Baylor College of Medicine

Researchers from Baylor College of Medicine, Stanford School of Medicine and collaborating institutions report today in the journal Nature that they have identified a molecule in the blood that is produced during exercise that can effectively reduce food intake and obesity in mice.

The findings improve our understanding of the physiological processes underlying the interaction between exercise and hunger.

“Regular exercise has been proven to help weight loss, regulate appetite, and improve metabolic profile, especially for overweight and obese people,” said co-corresponding author Dr. Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor.

“If we can understand the mechanism by which exercise produces these benefits, we’ll be closer to helping many people improve their health.”

“We wanted to understand how exercise works at the molecular level to reap some of its benefits,” says co-corresponding author Jonathan Long, MD, assistant professor of pathology at Stanford Medicine and a Stanford ChEM-H Institute Scholar (Chemistry, engineering and medicine for human health).

“For example, older or frail people who can’t get enough exercise may one day benefit from taking a drug that can help slow osteoporosis, heart disease, or other conditions.”

Xu, Long and their colleagues conducted extensive analyzes of blood plasma compounds from mice after intense treadmill running. The most significantly induced molecule was a modified amino acid called Lac-Phe. It is synthesized from lactate (a byproduct of strenuous exercise that is responsible for the burning sensation in muscles) and phenylalanine (an amino acid that is one of the building blocks of protein).

In mice with diet-induced obesity (which were fed a high-fat diet), a high dose of Lac-Phe suppressed food intake by approximately 50% compared to control mice over a 12-hour period without affecting their exercise or energy expenditure. When administered to the mice for 10 days, Lac-Phe reduced cumulative food intake and body weight (due to loss of body fat) and improved glucose tolerance.

This shows blood plasma
Researchers identified a molecule in the blood produced during exercise that can effectively reduce food intake and obesity in mice. Image is in the public domain

The researchers also identified an enzyme called CNDP2 that is involved in the production of Lac-Phe and showed that mice without this enzyme did not lose as much weight during an exercise regimen as a control group on the same exercise plan.

Interestingly, the team also found robust increases in plasma Lac-Phe levels after physical activity in racehorses and humans. Data from an exercise cohort in humans showed that sprint exercise caused the most dramatic increase in Lac-Phe plasma, followed by resistance training and then endurance training.

“This suggests that Lac-Phe is an ancient and conserved system that regulates diet and is associated with physical activity in many animal species,” Long said.

“Our next steps involve finding more details about how Lac-Phe mediates its effects in the body, including the brain,” Xu said. “Our goal is to learn to modulate this movement pathway for therapeutic interventions.”

About this exercise and news about neuroscience research

Author: press office
Source: Baylor College of Medicine
Contact: Press Office – Baylor College of Medicine
Image: The image is in the public domain

Original research: Closed access.
“An exercise-inducible metabolite that suppresses diet and obesity” by Jonathan Long et al. Nature

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Abstract

An exercise-inducible metabolite that suppresses diet and obesity

Exercise offers protection against obesity, type 2 diabetes and other cardiovascular diseases. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear.

Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signaling metabolite that suppresses nutrition and obesity.

The biosynthesis of Lac-Phe from lactate and phenylalanine takes place in CNDP2 cells, including macrophages, monocytes, and other immune and epithelial cells located in various organs. In diet-induced obese mice, pharmacologically-mediated increase in Lac-Phe reduces food intake without affecting exercise or energy expenditure.

Chronic administration of Lac-Phe reduces adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity after exercise training.

Finally, large activity-induced elevations in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species.

These data define a conserved exercise-induced metabolite that regulates food intake and influences systemic energy balance.

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