The benefits of exercise in a pill? Science is closer to this goal


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

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

“Regular exercise has been shown to help with weight loss, regulate appetite and improve metabolic profile, particularly in overweight and obese people,” said co-author Dr. Yong Xu, Professor of Pediatrics – Nutrition and Molecular and Cellular Biology at Baylor.

“If we can understand the mechanism by which exercise triggers these benefits, then we can bring many people closer to improving their health.”

“We wanted to understand how movement works at the molecular level in order to capture some of its benefits,” said co-corresponding author Jonathan Long, MD, an assistant professor of pathology at Stanford Medicine and Institute Scholar of Stanford ChEM-H (Chemistry, Engineering, and medicine for human health).

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

Xu, Long and their colleagues conducted comprehensive analyzes of blood plasma compounds from mice after intense treadmill running. The most strongly 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 proteins).

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

Researchers identified a molecule in the blood produced during exercise that can effectively reduce food intake and obesity in mice. The 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 lacking this enzyme did not lose as much weight on an exercise regimen as a control group on the same exercise regimen.

Interestingly, the team also found significant increases in plasma Lac-Phe levels after physical activity in both racehorses and humans. Data from a human exercise cohort showed that sprinting exercise induced the most dramatic increase in plasma Lac-Phe, followed by resistance training and then endurance training.

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

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

About this exercise and news from neuroscientific research

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

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

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An exercise-inducible metabolite that suppresses food intake and obesity

Exercise protects against obesity, type 2 diabetes and other cardiometabolic 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 food intake and obesity.

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

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

Finally, large activity-induced increases 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-inducible metabolite that controls food intake and affects systemic energy balance.

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