Cell · 2024
A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Moya-Garzon Maria Dolores, Wang Mengjie, Li Veronica L, Lyu Xuchao, Wei Wei, Tung Alan Sheng-Hwa, Raun Steffen H, Zhao Meng, Coassolo Laetitia, Islam Hashim, Oliveira Barbara, Dai Yuqin, Spaas Jan, Delgado-Gonzalez Antonio, Donoso Kenyi, Alvarez-Buylla Aurora, Franco-Montalban Francisco, Letian Anudari, Ward Catherine P, Liu Lichao, Svensson Katrin J, Goldberg Emily L, Gardner Christopher D, Little Jonathan P, Banik Steven M, Xu Yong, Long Jonathan Z
Аннотация
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.