New Ketone Metabolism Pathway Reveals Anti-Obesity Potential

Researchers have uncovered a previously unknown metabolic pathway in which β-hydroxybutyrate (BHB), a key ketone body, forms bioactive metabolites with amino acids through CNDP2-dependent enzymatic conjugation. This newly identified BHB shunt pathway produces BHB-amino acids, including BHB-Phe, which is ketosis-inducible and suppresses appetite by activating hypothalamic and brainstem neurons. Experiments in mice showed that disrupting CNDP2 eliminated this metabolic activity, leading to increased food intake and weight gain despite ketogenic diet interventions. Notably, this pathway is also conserved in humans, indicating its potential role in energy balance and obesity regulation. These findings expand our understanding of ketone metabolism and suggest new therapeutic avenues for obesity management through BHB-based metabolic modulation.