小窝蛋白-1在胎儿大脑代谢编程中的作用。

Role of caveolin-1 in metabolic programming of fetal brain.

作者信息

Islam Maliha, Behura Susanta K

机构信息

Division of Animal Sciences, 920 East Campus Drive, University of Missouri, Columbia, MO 65211, USA.

MU Institute for Data Science and Informatics, University of Missouri, Columbia, MO, USA.

出版信息

iScience. 2023 Aug 25;26(10):107710. doi: 10.1016/j.isci.2023.107710. eCollection 2023 Oct 20.

DOI:10.1016/j.isci.2023.107710

PMID:37720105

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10500482/

Abstract

Mice lacking caveolin-1 (), a key protein of plasma membrane, exhibit brain aging at an early adult stage. Here, integrative analyses of metabolomics, transcriptomics, epigenetics, and single-cell data were performed to test the hypothesis that metabolic deregulation of fetal brain due to the ablation of is linked to brain aging in these mice. The results of this study show that lack of caused deregulation in the lipid and amino acid metabolism in the fetal brain, and genes associated with these deregulated metabolites were significantly altered in the brain upon aging. Moreover, ablation of deregulated several metabolic genes in specific cell types of the fetal brain and impacted DNA methylation of those genes in coordination with mouse epigenetic clock. The findings of this study suggest that the aging program of brain is confounded by metabolic abnormalities in the fetal stage due to the absence of .

摘要

缺乏小窝蛋白-1（一种质膜关键蛋白）的小鼠在成年早期就表现出脑衰老。在此，进行了代谢组学、转录组学、表观遗传学和单细胞数据的综合分析，以检验因小窝蛋白-1缺失导致胎儿脑代谢失调与这些小鼠脑衰老相关的假说。本研究结果表明，小窝蛋白-1的缺失导致胎儿脑脂质和氨基酸代谢失调，与这些失调代谢物相关的基因在脑衰老时发生显著改变。此外，小窝蛋白-1的缺失使胎儿脑特定细胞类型中的几个代谢基因失调，并与小鼠表观遗传时钟协同影响这些基因的DNA甲基化。本研究结果表明，由于小窝蛋白-1缺失，胎儿期的代谢异常会混淆脑衰老进程。