健康和动脉粥样硬化条件下跨器官代谢物的产生和消耗，这一成果由美国加州大学Cholsoon Jang小组经过不懈努力而取得。该项研究成果发表在2025年5月27日出版的《细胞》上。
利用猪的动静脉代谢组学、组织转录组学和多种病理生理条件下的激素阵列，该课题组人员绘制了一幅10种跨器官代谢物产生和消耗的图谱，其中包括禁食/饲养、西方饮食和低密度脂蛋白受体（LDLR）缺乏引起的心血管疾病进展。研究人员发现了许多依赖于摄食和独立的代谢物产生和消耗器官的例子，并提出了这些被西方饮食通过改变代谢物浓度梯度和激素破坏的机制。西方饮食和LDLR缺乏都会触发肝外器官释放胆汁酸（BAs），可能导致循环BA水平异常升高，从而导致血管炎症和动脉粥样硬化的发展。这些研究揭示了在病理生理条件下复杂的器官间代谢串扰，为饮食影响和心脏代谢疾病提供了生化见解。
据介绍，哺乳动物的器官不断产生和消耗循环代谢物，以维持机体健康和生存。然而，这一基本过程的景观及其受饮食和疾病的干扰是未知的。
附：英文原文
Title: Cross-organ metabolite production and consumption in healthy and atherogenic conditions
Author: Hosung Bae, Sunhee Jung, Johnny Le, Ian Tamburini, Joohwan Kim, Eric Wang, Won-Suk Song, Wonsuk Choi, Ki-Hong Jang, Taekyung Kang, Miranda L. Lopez, Cuauhtemoc Ramirez, Ipsita Mohanty, Miranda E. Kelly, Jessie Kim, Raymond Kim, Sang Hee Park, Jongwon Baek, Bryan Mendez, Paul Petrus, Thomas Q. de Aguiar Vallim, Dequina A. Nicholas, Quinton Smith, Gina Lee, Marcus Seldin, Cholsoon Jang
Issue&Volume: 2025-05-27
Abstract: Mammalian organs continuously produce and consume circulating metabolites for organismal health and survival. However, the landscape of this fundamental process and its perturbation by diet and disease is unknown. Using arteriovenous metabolomics, tissue transcriptomics, and hormone arrays in multiple pathophysiological conditions in pigs, we generated an atlas of 10 cross-organ metabolite production and consumption during fasting/feeding, Western diet, and cardiovascular disease progression induced by low-density lipoprotein receptor (LDLR) deficiency. We discovered numerous instances of feeding-dependent and -independent metabolite production and consumption by organs and proposed mechanisms by which these are disrupted by Western diet via altered metabolite concentration gradients and hormones. Both Western diet and LDLR deficiency trigger the release of bile acids (BAs) by extra-hepatic organs, likely contributing to abnormally elevated circulating BA levels and consequent vascular inflammation and atherosclerosis development. These resources reveal intricate inter-organ metabolic crosstalk across pathophysiological conditions, offering biochemical insights into diet effects and cardiometabolic diseases.
DOI: 10.1016/j.cell.2025.05.001
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00512-4