Researchers from Baylor College of Medicine, Stanford University School of Medicine, and other institutions have discovered a new compound called BHB-Phe that regulates appetite and body weight. This finding was published in the journal Cell.
Previously, BHB was recognized as a liver-produced compound used for energy. Recent studies showed that BHB levels rise after fasting or exercise, sparking interest in its potential benefits for obesity and diabetes.
The study led by Dr. Jonathan Z. Long at Stanford University found that BHB is involved in another metabolic pathway where an enzyme named CNDP2 combines it with amino acids. The most prevalent of these compounds, BHB-Phe, influences metabolism and body weight in animal models.
Dr. Yong Xu's team 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 said. They discovered that BHB-Phe activates neurons in the hypothalamus and brainstem, reducing feeding and body weight. Mice lacking CNDP2 consumed more food and gained weight.
CNDP2 also produces Lac-Phe, a related compound known to reduce food intake during exercise. However, Xu noted differences between their effects: "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."
These findings suggest that disruptions in the pathway involving BHB-Phe could be linked to obesity and other conditions, warranting further research.
"This work opens up many new possibilities," Long stated. "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."
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