小柯机器人

蛋白质-代谢物关联研究揭示了人血浆代谢物新蛋白质组学的决定因素，这一成果由美国以色列女执事医疗中心Robert E. Gerszten团队经过不懈努力而取得。相关论文发表在2023年8月14日出版的《细胞-代谢》杂志上。

研究人员对来自三个人类队列的3，626个血浆样本进行了蛋白质-代谢物关联研究。研究人员检测到存在1，265种蛋白质和365种代谢物之间171，800种明显的蛋白质-代谢物对应关性，包括代谢和信号通路（如蛋白质甲状腺素结合球蛋白和甲状腺素代谢物）中的既定关系，以及数千种新关系。在孟德尔随机化（MR）分析中，研究确定了假定蛋白与代谢物间的因果关联。

研究人员在三种关键蛋白调节因子敲除的小鼠中验证了血浆代谢组学发现的高MR关联。这些分析确定了人血浆中生物活性蛋白质和代谢物之间以前未知的关联，并提供了公开可用的数据以便对人类新陈代谢和疾病进行研究。

据介绍，虽然使用高通量生化分析已经鉴定出许多新的基因-代谢物和基因-蛋白质关联，但缺乏利用人类遗传学来阐明循环蛋白质和代谢物之间因果关系的系统研究。

附：英文原文

Title: Protein-metabolite association studies identify novel proteomic determinants of metabolite levels in human plasma

Author: Mark D. Benson, Aaron S. Eisman, Usman A. Tahir, Daniel H. Katz, Shuliang Deng, Debby Ngo, Jeremy M. Robbins, Alissa Hofmann, Xu Shi, Shuning Zheng, Michelle Keyes, Zhi Yu, Yan Gao, Laurie Farrell, Dongxiao Shen, Zsu-Zsu Chen, Daniel E. Cruz, Mario Sims, Adolfo Correa, Russell P. Tracy, Peter Durda, Kent D. Taylor, Yongmei Liu, W. Craig Johnson, Xiuqing Guo, Jie Yao, Yii-Der Ida Chen, Ani W. Manichaikul, Deepti Jain, Qiong Yang, Claude Bouchard, Mark A. Sarzynski, Stephen S. Rich, Jerome I. Rotter, Thomas J. Wang, James G. Wilson, Clary B. Clish, Indra Neil Sarkar, Pradeep Natarajan, Robert E. Gerszten

Issue&Volume: 2023-08-14

Abstract: Although many novel gene-metabolite and gene-protein associations have been identifiedusing high-throughput biochemical profiling, systematic studies that leverage humangenetics to illuminate causal relationships between circulating proteins and metabolitesare lacking. Here, we performed protein-metabolite association studies in 3,626 plasmasamples from three human cohorts. We detected 171,800 significant protein-metabolitepairwise correlations between 1,265 proteins and 365 metabolites, including establishedrelationships in metabolic and signaling pathways such as the protein thyroxine-bindingglobulin and the metabolite thyroxine, as well as thousands of new findings. In Mendelianrandomization (MR) analyses, we identified putative causal protein-to-metabolite associations.We experimentally validated top MR associations in proof-of-concept plasma metabolomicsstudies in three murine knockout strains of key protein regulators. These analysesidentified previously unrecognized associations between bioactive proteins and metabolitesin human plasma. We provide publicly available data to be leveraged for studies inhuman metabolism and disease.

DOI: 10.1016/j.cmet.2023.07.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00271-1

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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