Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins
Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins
复制标题
DOI：
10.1016/j.cmet.2022.12.004
复制
发表时间：
2023-01-03
期刊：
影响因子：
29
通讯作者：
Barnes, Christopher A.
中科院分区：
文献类型：
--
作者：
Martinez, Thomas F.;Lyons-Abbott, Sally;Barnes, Christopher A.
微生物蛋白 (MP) 是未知代谢调节因子的潜在丰富来源。在这里，我们使用核糖体分析 (Ribo-seq) 在原代棕色、白色和米色小鼠脂肪细胞中筛选出 3,877 个未注释的 MP 编码小 ORF (smORF)。其中，我们通过蛋白质组学验证了 85 个 MP，其中包括小鼠血浆中的 33 个循环 MP。对不同生理条件（高脂饮食）下 MP 编码 mRNA 的分析表明，大量 MP 在体内脂肪组织中受到调节，并与已建立的代谢基因共表达。此外，Ribo-seq 为 Gm8773 的翻译提供了证据，Gm8773 编码与人类和鸡 FAM237B 同源的分泌性 MP。 Gm8773 在下丘脑的弓状核中高度表达，脑室内给予重组 mFAM237B 在肥胖小鼠中显示出促食欲活性。总之，这些数据凸显了该脂肪细胞 MP 数据库在识别 MP 在基本代谢和生理过程（例如进食）中的作用方面的价值。
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.