小柯机器人

美国哈佛医学院Edward T. Chouchani等研究人员合作利用棕色脂肪蛋白质组的结构定义出代谢生理学的调节因子。2022年11月4日，《细胞》杂志在线发表了这项成果。

研究人员对163只遗传定义的多样性远交系小鼠的棕色脂肪组织（BAT）进行了深入的定量蛋白质组学研究，这个模型与人类的遗传和表型变化相类似。研究人员利用这种多样性来定义了远交系小鼠蛋白质组的功能结构，包括10479个蛋白质。研究人员为2578个蛋白质分配了合作功能，从而能够系统地发现BAT的调节因子。研究人员还确定了638个与保护代谢疾病或对至少一个参数的敏感性相关的蛋白质。

研究人员利用这些发现揭示了SFXN5、LETMD1和ATP1A2作为BAT产热或脂肪的调节因子，并提供了OPABAT作为一种资源来了解BAT调节代谢生理学的保守机制。

据介绍，BAT调节着代谢生理学。然而，几乎所有关于BAT蛋白功能的机制研究都发生在单一的近交系小鼠品系中，这限制了对BAT调节生理学的通用机制的理解。

附：英文原文

Title: Architecture of the outbred brown fat proteome defines regulators of metabolic physiology

Author: Haopeng Xiao, Luiz H.M. Bozi, Yizhi Sun, Christopher L. Riley, Vivek M. Philip, Mandy Chen, Jiaming Li, Tian Zhang, Evanna L. Mills, Margo P. Emont, Wenfei Sun, Anita Reddy, Ryan Garrity, Jiani Long, Tobias Becher, Laura Potano Vitas, Dina Laznik-Bogoslavski, Martha Ordonez, Xinyue Liu, Xiong Chen, Yun Wang, Weihai Liu, Nhien Tran, Yitong Liu, Yang Zhang, Aaron M. Cypess, Andrew P. White, Yuchen He, Rebecca Deng, Heiko Schder, Joao A. Paulo, Mark P. Jedrychowski, Alexander S. Banks, Yu-Hua Tseng, Paul Cohen, Linus T. Tsai, Evan D. Rosen, Samuel Klein, Maria Chondronikola, Fiona E. McAllister, Nick Van Bruggen, Edward L. Huttlin, Bruce M. Spiegelman, Gary A. Churchill, Steven P. Gygi, Edward T. Chouchani

Issue&Volume: 2022-11-04

Abstract: Brown adipose tissue (BAT) regulates metabolic physiology. However, nearly all mechanisticstudies of BAT protein function occur in a single inbred mouse strain, which has limitedthe understanding of generalizable mechanisms of BAT regulation over physiology. Here,we perform deep quantitative proteomics of BAT across a cohort of 163 geneticallydefined diversity outbred mice, a model that parallels the genetic and phenotypicvariation found in humans. We leverage this diversity to define the functional architectureof the outbred BAT proteome, comprising 10,479 proteins. We assign co-operative functionsto 2,578 proteins, enabling systematic discovery of regulators of BAT. We also identify638 proteins that correlate with protection from, or sensitivity to, at least oneparameter of metabolic disease. We use these findings to uncover SFXN5, LETMD1, andATP1A2 as modulators of BAT thermogenesis or adiposity, and provide OPABAT as a resourcefor understanding the conserved mechanisms of BAT regulation over metabolic physiology.

DOI: 10.1016/j.cell.2022.10.003

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01318-6