Research has revealed a new metabolic pathway involving beta-hydroxybutyric acid (BHB). Previously known as a liver-produced fuel, BHB is now found to be attached to amino acids by the enzyme CNDP2. The most abundant BHB amino acid, N-β-hydroxybutyryl phenylalanine (BHB-Phe), can impact body weight and metabolism in animal models.
Beta-hydroxybutyric acid (BHB) is an abundant ketone body. All BHB metabolic pathways known to date involve the interconversion of BHB and primary energy intermediates. Moya Garzon others. BHB et al. identified a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic binding of BHB and free amino acids. Image credit: Moya-Garzon others., doi: 10.1016/j.cell.2024.10.032.
Mammals have developed intricate nutrient response pathways linking external energy sources with internal metabolic balance.
These pathways involve changes in cellular energy metabolites serving as both fuel sources and downstream regulators.
BHB, a ketone body, is a key example whose levels rise during low carbohydrate conditions like starvation, intermittent fasting, or ketogenic diet.
In a recent study, Professor Yong Xu of Baylor College of Medicine and team investigated how BHB-Phe, the most common BHB amino acid, affects eating habits and body weight in mice.
“Brain neuron groups regulate feeding behavior, so we mapped the brain to identify regions activated by BHB-Phe,” explained Professor Xu.
“BHB-Phe activated neural populations in the hypothalamus and brainstem, suppressing feeding and leading to weight loss.”
In contrast, mice lacking CNDP2 enzyme, deficient in BHB-Phe, ate more and gained weight.
Interestingly, CNDP2 also produces Lac-Phe, a compound discovered earlier by the research team.
“Lac-Phe from exercise can reduce food intake and obesity in mice,” added Professor Xu.
“But do Lac-Phe and BHB-Phe trigger effects by activating the same brain neurons?”
This discovery points to a possible disruption of the BHB-Phe pathway, present in humans, in obesity and other conditions, warranting further research to understand the mechanism.
“This study unveils new prospects,” commented Dr. Jonathan Long from Stanford.
“In the future, using BHB-Phe to promote weight loss without carbohydrate restrictions may be feasible.”
Featured in this week’s cell journal.
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Maria Dolores Moya-Garzon others. The β-hydroxybutyrate shunt pathway produces anti-obesity ketone metabolites. cell published online on November 12, 2024. doi: 10.1016/j.cell.2024.10.032
Source: www.sci.news
