Novel Molecule BHB-Phe Could Revolutionize Obesity Treatment

The discovery of BHB-Phe, a novel molecule produced by the body that regulates hunger and body weight through interactions with neurons in the brain, has been described in the journal Cell by researchers from Baylor College of Medicine, Stanford University School of Medicine, and other institutions (1^✔ ✔Trusted Source
A β-hydroxybutyrate shunt pathway generates antiobesity ketone metabolites

Go to source).

Advertisement

What is BHB-Phe?

Until today, BHB-Phe was known as a chemical produced by the liver for use as fuel. However, in recent years, scientists have discovered that BHB levels rise in the body after fasting or exercise, sparking interest in researching potential positive applications in obesity and diabetes.

In the current study, Stanford University researchers led by co-corresponding author Dr. Jonathan Z. Long, an associate professor of pathology, showed that BHB also interacts with another metabolic pathway.

In this situation, an enzyme called CNDP2 converts BHB into amino acids. In addition, the most abundant BHB-amino acid, BHB-Phe, can alter body weight and metabolism in animal models.

Advertisement

Does BHB-Phe Affect Hunger and Body Weight?

The Baylor team, led by co-corresponding author Dr. Yong Xu, professor of pediatrics - nutrition and associate director of basic sciences at the USDA/ARS Children's Nutrition Research Center at Baylor, investigated how BHB-Phe affects feeding behavior and body weight in mice.

"We know that groups of neurons in the brain regulate feeding behavior, so we mapped the entire brain to determine which areas were activated by BHB-Phe," Xu told me.

Advertisement

How Does BHB-Phe Help to Suppress Body Weight?

"We discovered that BHB-Phe activates neuronal populations in the hypothalamus and brainstem, which suppresses hunger and lowers body weight. In contrast, mice that were genetically engineered to not make CNDP2 and hence lack BHB-Phe ate more and gained weight.

Interestingly, the CNDP2 enzyme that makes BHB-Phe also creates a similar molecule known as Lac-Phe, which the authors previously found. According to the researchers in Nature, Lac-Phe is a molecule in the blood created during exercise that can lower food intake and obesity in mice. But do Lac-Phe and BHB-Phe share similar effects by activating the same neurons in the brain?

"Our analyses showed that only a small proportion of neurons were activated by both compounds; most of the neurons activated by Lac-Phe and BHB-Phe were different," says Xu. "This indicates the possibility that, although both compounds affect feeding behaviors in similar ways, they mediate this effect by different mechanisms."

The findings imply that the novel pathway involving BHB-Phe, which is also present in humans, may be disrupted in obesity and maybe other disorders, highlighting the need for additional research to better understand the mechanism.

"This work opens up many new possibilities," Long told the audience. "For example, it might be possible for people in the future to consume BHB-Phe to drive weight loss without restricting carbohydrates in their diet."

Reference:

1. A β-hydroxybutyrate shunt pathway generates antiobesity ketone metabolites - (https://www.cell.com/cell/pdf/S0092-8674(24)01214-5.pdf)

Source-Medindia