Maria Dolores Moya-Garzon, Mengjie Wang, Veronica L. Li, Xuchao Lyu, Wei Wei, Alan Sheng-Hwa Tung, Steffen H. Raun, Meng Zhao, Laetitia Coassolo, Hashim Islam, Barbara Oliveira, Yuqin Dai, Jan Spaas, Antonio Delgado-Gonzalez, Kenyi Donoso, Aurora Alvarez-Buylla, Francisco Franco-Montalban, Anudari Letian, Catherine P. Ward, Lichao Liu, Katrin J. Svensson, Emily L. Goldberg, Christopher D. Gardner, Jonathan P. Little, Steven M. Banik, Yong Xu, Jonathan Z. Long

This study identifies a previously uncharacterized secondary metabolic pathway of β-hydroxybutyrate (BHB), a key ketone body, through its enzymatic conjugation with amino acids by CNDP2. The resulting BHB-amino acids, including BHB-Phenylalanine (BHB-Phe), are shown to have anti-obesity effects in mice, including reducing food intake and body weight. The findings highlight the role of this pathway in energy balance and its conservation across mice and humans. This research not only expands our understanding of ketone metabolism but also uncovers potential therapeutic targets for obesity and metabolic disorders.