美国西雅图诺和诺德研究中心Christopher A. Barnes和美国索尔克生物研究所Alan Saghatelian共同合作，近期取得重要工作进展。他们通过对小鼠棕色和白色脂肪细胞进行分析来确定与代谢有关的小ORF和功能性微蛋白。相关研究成果2023年1月3日在线发表于《细胞—代谢》杂志上。

据介绍，微蛋白（MP）是一种潜在的非典型代谢调节剂的丰富来源。

研究人员使用核糖体分析（Ribo-seq）在原代棕色、白色和米色小鼠脂肪细胞中对3877个未标记的MP编码小ORF（smORF）进行了整理。其中，研究人员通过蛋白质组学验证了85个MP，包括小鼠血浆中的33个循环MP。在不同生理条件（高脂肪饮食）下对MP编码mRNA的分析表明，体内脂肪组织中调节了大量MP，并与已建立的代谢基因共同表达。

此外，Ribo-seq为Gm8773的翻译提供了证据，该基因编码与人和鸡FAM237B同源的分泌MP。Gm8773在下丘脑弓状核中高度表达，侧脑室内注射重组mFAM237B在肥胖小鼠中显示出促食欲活性。

总之，这些数据强调了脂肪细胞MP数据库在识别MP在基础代谢和生理过程（如喂养）中作用方面的价值。

附：英文原文

Title: Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins

Author: Thomas F. Martinez, Sally Lyons-Abbott, Angie L. Bookout, Eduardo V. De Souza, Cynthia Donaldson, Joan M. Vaughan, Calvin Lau, Ariel Abramov, Arian F. Baquero, Karalee Baquero, Dave Friedrich, Justin Huard, Ray Davis, Bong Kim, Ty Koch, Aaron J. Mercer, Ayesha Misquith, Sara A. Murray, Sakara Perry, Lindsay K. Pino, Christina Sanford, Alex Simon, Yu Zhang, Garrett Zipp, Cristiano V. Bizarro, Maxim N. Shokhirev, Andrew J. Whittle, Brian C. Searle, Michael J. MacCoss, Alan Saghatelian, Christopher A. Barnes

Issue&Volume: 2023/01/03

Abstract: Microproteins (MPs) are a potentially rich source of uncharacterized metabolic regulators. Here, we use ribosome profiling (Ribo-seq) to curate 3,877 unannotated MP-encoding small ORFs (smORFs) in primary brown, white, and beige mouse adipocytes. Of these, we validated 85 MPs by proteomics, including 33 circulating MPs in mouse plasma. Analyses of MP-encoding mRNAs under different physiological conditions (high-fat diet) revealed that numerous MPs are regulated in adipose tissue in vivo and are co-expressed with established metabolic genes. Furthermore, Ribo-seq provided evidence for the translation of Gm8773, which encodes a secreted MP that is homologous to human and chicken FAM237B. Gm8773 is highly expressed in the arcuate nucleus of the hypothalamus, and intracerebroventricular administration of recombinant mFAM237B showed orexigenic activity in obese mice. Together, these data highlight the value of this adipocyte MP database in identifying MPs with roles in fundamental metabolic and physiological processes such as feeding.

DOI: 10.1016/j.cmet.2022.12.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00541-1