明日6/11担当の野口（神経科学研究部 訪問研究員/東京ガスグループ 産業医）
です。 明日は、下記の論文を紹介させて頂く予定です。
A beta-hydroxybutyrate shunt pathway generates anti-obesity ketone
metabolites.
Moya-Garzon MD, Wang M, Li VL, Lyu X, Wei W, Tung AS, Raun SH, Zhao M,
Coassolo L, Islam H, Oliveira B, Dai Y, Spaas J, Delgado-Gonzalez A,
Donoso K, Alvarez-Buylla A, Franco-Montalban F, Letian A, Ward CP, Liu L,
Svensson KJ, Goldberg EL, Gardner CD, Little JP, Banik SM, Xu Y, Long
JZ.
Cell. 2025 Jan 9;188(1):175-186.e20. doi: 10.1016/j.cell.2024.10.032.
Epub 2024 Nov 12. PMID: 39536746
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.