@misc{10481/107504,
year = {2025},
month = {1},
url = {https://hdl.handle.net/10481/107504},
abstract = {β-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids. This BHB shunt pathway generates a family of anti-obesity ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. The most abundant BHB-amino acid, BHB-Phe, is a ketosis-inducible congener of Lac-Phe that activates hypothalamic and brainstem neurons and suppresses feeding. Conversely, CNDP2-KO mice exhibit increased food intake and body weight following exogenous ketone ester supplementation or a ketogenic diet. CNDP2-dependent amino acid BHB-ylation and BHB-amino acid metabolites are also conserved in humans. Therefore, enzymatic amino acid BHB-ylation defines a ketone shunt pathway and bioactive ketone metabolites linked to energy balance.},
organization = {Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA},
keywords = {BHB},
keywords = {metabolomics},
keywords = {enzyme},
keywords = {obesity},
keywords = {ketone},
keywords = {metabolite},
title = {A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites},
doi = {10.1016/j.cell.2024.10.032},
author = {Moya-Garzon, Maria Dolores and Wang, Mengjie and Li, Veronica L. and Lyu, Xuchao and Wei, Wei and Tung, Alan Sheng-Hwa and Raun, Steffen H. and Zhao, Meng and Coassolo, Laetitia and Islam, Hashim and Oliveira, Barbara and Dai, Yuqin and Spaas, Jan and Delgado-Gonzalez, Antonio and Donoso, Kenyi and Alvarez-Buylla, Aurora and Franco-Montalban, Francisco and Anudari, Anudari and Ward, Catherine P. and Liu, Lichao and Svensson, Katrin J. and Goldberg, Emily L. and Gardner, Christopher D. and Little, Jonathan P. and Banik, Steven M. and Xu, Yong and Long, Jonathan Z.},
}